Diet alters performance and transcription patterns in Oedaleus asiaticus (Orthoptera: Acrididae) grasshoppers.

Science.gov (United States)

Huang, Xunbing; Whitman, Douglas W; Ma, Jingchuan; McNeill, Mark Richard; Zhang, Zehua

2017-01-01

We reared Oedaleus asiaticus grasshoppers under four different single-plant diets to examine the relationships among diet, performance, stress, and transcription patterns. Grasshoppers fed only Artemisia frigida (Asteraceae) were stressed, as indicated by their lower growth, size, development, and survival, in comparison to grasshoppers fed on any of three grasses, Cleistogenes squarrosa, Leymus chinensis, or Stipa krylovii (all Poaceae). We then used transcriptome analysis to examine how gene expression levels in O. asiaticus were altered by feeding on these diets. Nymphs fed A. frigida had the largest variation in gene expression profiles with a total of 299 genes significantly up- or down-regulated compared to those feeding on the three grasses: down-regulated genes included those involved in cuticle biosynthesis, DNA replication, biosynthesis and metabolism of nutrition. The up-regulated genes included stress-resistant and detoxifying enzymes. GO and KEGG enrichment analysis also showed that feeding on A. frigida could down-regulate biosynthesis and metabolism related pathways, and up-regulate stress-resistant and detoxification terms and pathways. Our results show that diet significantly altered gene-expression, and that unfavorable, stressful diets induce more transcriptional changes than favorable diets. Altered gene-expression represents phenotypic plasticity, and many such changes appear to be evolved, adaptive responses. The ease and regularity by which individuals shift phenotypes via altered transcription suggests that populations consist not of similar, fixed phenotypes, but of a collection of ever-changing, divergent phenotypes.

Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

Directory of Open Access Journals (Sweden)

Shinya Akatsuka

Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

Induced defences alter the strength and direction of natural selection on reproductive traits in common milkweed.

Science.gov (United States)

Thompson, K A; Cory, K A; Johnson, M T J

2017-06-01

Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defences can alter natural selection on reproductive traits, but it is unclear whether induced defences will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca L., we induced plant defences using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), whereas control plants only experienced a trend towards selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defences can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defences may promote the evolution of plant reproductive diversity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics

Directory of Open Access Journals (Sweden)

Isak Demirel

2017-06-01

Full Text Available It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL-producing UPEC (ESBL019 during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array. All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-α from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce TNF-α release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.

Femtosecond laser-induced herringbone patterns

Science.gov (United States)

Garcell, Erik M.; Lam, Billy; Guo, Chunlei

2018-06-01

Femtosecond laser-induced herringbone patterns are formed on copper (Cu). These novel periodic structures are created following s-polarized, large incident angle, femtosecond laser pulses. Forming as slanted and axially symmetric laser-induced periodic surface structures along the side walls of ablated channels, the result is a series of v-shaped structures that resemble a herringbone pattern. Fluence mapping, incident angle studies, as well as polarization studies have been conducted and provide a clear understanding of this new structure.

Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

Directory of Open Access Journals (Sweden)

Magdalena M Przybycien-Szymanska

2011-04-01

Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

Science.gov (United States)

Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

2009-01-01

Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

Alteration of gene conversion patterns in Sordaria fimicola by supplementation with DNA bases.

Science.gov (United States)

Kitani, Y; Olive, L S

1970-08-01

Supplementation with DNA bases in crosses of Sordaria fimicola heterozygous for spore color markers (g(1), h(2)) within the gray-spore (g) locus has been found to cause significant alterations in patterns of gene conversion at the two mutant sites. Each base had its own characteristic effect in altering the conversion pattern, and responses of the two mutant sites to the four bases were different in several ways. Also, the responses of the two involved chromatids of the meiotic bivalent were different.

Genetic and epigenetic alterations induced by different levels of rye genome integration in wheat recipient.

Science.gov (United States)

Zheng, X L; Zhou, J P; Zang, L L; Tang, A T; Liu, D Q; Deng, K J; Zhang, Y

2016-06-17

The narrow genetic variation present in common wheat (Triticum aestivum) varieties has greatly restricted the improvement of crop yield in modern breeding systems. Alien addition lines have proven to be an effective means to broaden the genetic diversity of common wheat. Wheat-rye addition lines, which are the direct bridge materials for wheat improvement, have been wildly used to produce new wheat cultivars carrying alien rye germplasm. In this study, we investigated the genetic and epigenetic alterations in two sets of wheat-rye disomic addition lines (1R-7R) and the corresponding triticales. We used expressed sequence tag-simple sequence repeat, amplified fragment length polymorphism, and methylation-sensitive amplification polymorphism analyses to analyze the effects of the introduction of alien chromosomes (either the entire genome or sub-genome) to wheat genetic background. We found obvious and diversiform variations in the genomic primary structure, as well as alterations in the extent and pattern of the genomic DNA methylation of the recipient. Meanwhile, these results also showed that introduction of different rye chromosomes could induce different genetic and epigenetic alterations in its recipient, and the genetic background of the parents is an important factor for genomic and epigenetic variation induced by alien chromosome addition.

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo

Science.gov (United States)

Fisher, Jonathan A. N.; Gumenchuk, Iryna

2018-06-01

Objective. The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam’s focus. Approach. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca2+ responses. Main results. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm‑2 (I sppa), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca2+ responses. Significance. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo.

Science.gov (United States)

Fisher, Jonathan A N; Gumenchuk, Iryna

2018-02-13

The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam's focus. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca 2+ responses. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm -2 (I sppa ), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca 2+ responses. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

Membrane alterations induced by nonstructural proteins of human norovirus.

Directory of Open Access Journals (Sweden)

Sylvie Y Doerflinger

2017-10-01

Full Text Available Human noroviruses (huNoV are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4 variants. The viral nonstructural (NS proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV. Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER which included single membrane vesicles (SMVs, double membrane vesicles (DMVs and multi membrane vesicles (MMVs. In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

Science.gov (United States)

Bhattacharya, Sharmila; Hosamani, Ravikumar

2015-01-01

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Altered movement patterns and muscular activity during single and double leg squats in individuals with anterior cruciate ligament injury.

Science.gov (United States)

Trulsson, Anna; Miller, Michael; Hansson, Gert-Åke; Gummesson, Christina; Garwicz, Martin

2015-02-13

Individuals with Anterior Cruciate Ligament (ACL) injury often show altered movement patterns, suggested to be partly due to impaired sensorimotor control. Here, we therefore aimed to assess muscular activity during movements often used in ACL-rehabilitation and to characterize associations between deviations in muscular activity and specific altered movement patterns, using and further exploring the previously developed Test for substitution Patterns (TSP). Sixteen participants (10 women) with unilateral ACL rupture performed Single and Double Leg Squats (SLS; DLS). Altered movement patterns were scored according to TSP, and Surface Electromyography (SEMG) was recorded bilaterally in six hip, thigh and shank muscles. To quantify deviations in muscular activity, SEMG ratios were calculated between homonymous muscles on injured and non-injured sides, and between antagonistic muscles on the same side. Correlations between deviations of injured/non-injured side SEMG ratios and specific altered movement patterns were calculated. Injured/non-injured ratios were low at transition from knee flexion to extension in quadriceps in SLS, and in quadriceps and hamstrings in DLS. On injured side, the quadriceps/hamstrings ratio prior to the beginning of DLS and end of DLS and SLS, and tibialis/gastrocnemius ratio at end of DLS were lower than on non-injured side. Correlations were found between specific altered movement patterns and deviating muscular activity at transition from knee flexion to extension in SLS, indicating that the more deviating the muscular activity on injured side, the more pronounced the altered movement pattern. "Knee medial to supporting foot" correlated to lower injured/non-injured ratios in gluteus medius (rs = -0.73, p = 0.001), "lateral displacement of hip-pelvis-region" to lower injured/non-injured ratios in quadriceps (rs = -0.54, p = 0.03) and "displacement of trunk" to higher injured/non-injured ratios in gluteus medius (rs = 0.62, p = 0

Genetic alterations during radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Kodama, Seiji

1995-01-01

This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

Aging induced ER stress alters sleep and sleep homeostasis

OpenAIRE

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2013-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical ...

Evaluation of Spatial Pattern of Altered Flow Regimes on a River Network Using a Distributed Hydrological Model.

Science.gov (United States)

Ryo, Masahiro; Iwasaki, Yuichi; Yoshimura, Chihiro; Saavedra V, Oliver C

2015-01-01

Alteration of the spatial variability of natural flow regimes has been less studied than that of the temporal variability, despite its ecological importance for river ecosystems. Here, we aimed to quantify the spatial patterns of flow regime alterations along a river network in the Sagami River, Japan, by estimating river discharge under natural and altered flow conditions. We used a distributed hydrological model, which simulates hydrological processes spatiotemporally, to estimate 20-year daily river discharge along the river network. Then, 33 hydrologic indices (i.e., Indicators of Hydrologic Alteration) were calculated from the simulated discharge to estimate the spatial patterns of their alterations. Some hydrologic indices were relatively well estimated such as the magnitude and timing of maximum flows, monthly median flows, and the frequency of low and high flow pulses. The accuracy was evaluated with correlation analysis (r > 0.4) and the Kolmogorov-Smirnov test (α = 0.05) by comparing these indices calculated from both observed and simulated discharge. The spatial patterns of the flow regime alterations varied depending on the hydrologic indices. For example, both the median flow in August and the frequency of high flow pulses were reduced by the maximum of approximately 70%, but these strongest alterations were detected at different locations (i.e., on the mainstream and the tributary, respectively). These results are likely caused by different operational purposes of multiple water control facilities. The results imply that the evaluation only at discharge gauges is insufficient to capture the alteration of the flow regime. Our findings clearly emphasize the importance of evaluating the spatial pattern of flow regime alteration on a river network where its discharge is affected by multiple water control facilities.

Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

Science.gov (United States)

Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

2017-09-01

Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

Science.gov (United States)

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-01-01

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

Science.gov (United States)

Engberg, G; Kling-Petersen, T; Nissbrandt, H

1993-11-01

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

Science.gov (United States)

Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

2016-09-01

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.

Science.gov (United States)

Sasaki, Au; Hasegawa, Naoya; Adachi, Kazunori; Sakagami, Hiroshi; Suda, Naoto

2017-10-01

The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg -1 ·day -1 ) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg -1 ·day -1 ) of aspirin or acetaminophen (300 mg·kg -1 ·day -1 ) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation. NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal

Image-Guided Analyses Reveal that Non-CD4 Splenocytes Contribute to CD4+ T Cell–Mediated Inflammation Leading to Islet Destruction by Altering Their Local Function and Not Systemic Trafficking Patterns

Directory of Open Access Journals (Sweden)

Mi-Heon Lee

2007-11-01

Full Text Available Recruitment of CD4+ T cells into islets is a critical component of islet inflammation (insulitis leading to type 1 diabetes; therefore, determining if conditions used to treat diabetes change their trafficking patterns is relevant to the outcome. Cotransfer of CD4+BDC2.5 (BDC cells with non-CD4 splenocytes obtained from newly diabetic NOD mice, but not when they are transferred alone, induces accelerated diabetes. It is unclear whether these splenocytes affect diabetes development by altering the systemic and/or local trafficking and proliferation patterns of BDC cells in target and nontarget tissues. To address these questions, we developed an animal model to visualize BDC cell trafficking and proliferation using whole-body in vivo bioluminescence imaging and used the images to direct tissue sampling for further analyses of the cell distribution within tissues. The whole-body, or macroscopic, trafficking patterns were not dramatically altered in both groups of recipient mice. However, the local patterns of cell distribution were distinct, which led to invasive insulitis only in cotransferred mice with an increased number of islet-infiltrating CD11b+ and CD11c+ cells. Taken together, the non-CD4 splenocytes act locally by promoting invasive insulitis without altering the systemic trafficking patterns or proliferation of BDC cells and thus contributing to diabetes by altering the localization within the tissue.

Tooth alterations in areas of bisphosphonate-induced osteonecrosis.

Science.gov (United States)

de Camargo Moraes, Paulo; Silva, Carolina Amália Barcellos; Soares, Andresa Borges; Passador-Santos, Fabrício; Corrêa, Maria Elvira Pizzigatti; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

2015-03-01

Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis. Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope. The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %). Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications. It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

Radiation-induced epigenetic alterations after low and high LET irradiations

International Nuclear Information System (INIS)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-01-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

Radiation-induced epigenetic alterations after low and high LET irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2011-02-10

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.

Science.gov (United States)

Veazey, Kylee J; Wang, Haiqing; Bedi, Yudhishtar S; Skiles, William M; Chang, Richard Cheng-An; Golding, Michael C

2017-05-01

Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program. To address this question, we examined the impact of ethanol exposure in mouse embryonic stem cells cultured under 2i conditions, where the transcriptional program is rigidly enforced through the use of small molecule inhibitors. We find that ethanol-induced changes in post-translational histone modifications are dose-dependent, unique to the chromatin modification under investigation, and that the extent and direction of the change differ between the period of exposure and the recovery phase. Similar to in vivo models, we find post-translational modifications affecting histone 3 lysine 9 are the most profoundly impacted, with the signature of exposure persisting long after alcohol has been removed. These changes in chromatin structure associate with dose-dependent alterations in the levels of transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin template do not consistently associate with changes in gene transcription, impede the process of differentiation, or affect the acquisition of monoallelic patterns of expression for the imprinted gene Igf2R. These findings question the inferred universal relevance of epigenetic changes induced by drugs of abuse and suggest that changes

Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativa L.).

Science.gov (United States)

Ou, Xiufang; Zhang, Yunhong; Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

2012-01-01

DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

Science.gov (United States)

Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R

2017-05-01

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

The alteration of chromatin domains during damage repair induced by ionizing radiation

International Nuclear Information System (INIS)

Cress, A.E.; Olson, K.M.; Olson, G.B.

1995-01-01

Several groups previously have reported the ability of chromatin structure to influence the production of damage induced by ionizing radiation. The authors' interest has been to determine whether chromatin structural alterations exist after ionizing radiation during a repair interval. The earlier work investigated this question using biochemical techniques. The crosslinking of nuclear structural proteins to DNA after ionizing radiation was observed. In addition, they found that the chromatin structure in vitro as measured by sucrose density gradient sedimentation, was altered after ionizing radiation. These observations added to earlier studies in which digital imaging techniques showed an alteration in feulgen-positive DNA after irradiation prompted the present study. The object of this study was to detect whether the higher order structure of DNA into chromatin domains within interphase human cells was altered in interphase cells in response to a radiation induced damage. The present study takes advantage of the advances in the detection of chromatin domains in situ using DNA specific dyes and digital image processing of established human T and B cell lines

Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

Science.gov (United States)

Goundadkar, Basavaraj B; Katti, Pancharatna

2017-09-01

The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (Pswimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease

Directory of Open Access Journals (Sweden)

Constanza Bondar

2017-01-01

Full Text Available Gaucher disease (GD is caused by mutations in the glucosylceramidase β (GBA 1 gene that confer a deficient level of activity of glucocerebrosidase (GCase. This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood. The bone tissue homeostasis is maintained by a balance between resorption of old bone by osteoclasts and new bone formation by osteoblasts. A central player in this balance is the osteocyte as it controls both processes. We studied the involvement of osteocytes in an in vitro chemical model of Gaucher disease. The osteocyte cell line MLO-Y4 was exposed to conduritol-β-epoxide (CBE, an inhibitor of GCase, for a period of 7, 14 and 21 days. Conditioned media from CBE-treated osteocytes was found to induce osteoclast differentiation. GCase inhibition caused alterations in Cx43 expression and distribution pattern and an increase in osteocyte apoptosis. Osteoclast differentiation involved osteocyte apoptotic bodies, receptor activator of nuclear factor κ-B ligand (RANKL and soluble factors. Thus, our results indicate that osteocytes may have a role to play in the bone pathophysiology of GD.

Microcirculation alterations in experimentally induced gingivitis in dogs.

Science.gov (United States)

Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

2017-01-01

The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

Distal-less induces elemental color patterns in Junonia butterfly wings.

Science.gov (United States)

Dhungel, Bidur; Ohno, Yoshikazu; Matayoshi, Rie; Iwasaki, Mayo; Taira, Wataru; Adhikari, Kiran; Gurung, Raj; Otaki, Joji M

2016-01-01

The border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. For two decades, it has been hypothesized that transcription factors such as Distal-less (Dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. In particular, it has been suggested that Dll is a determinant for eyespot size. However, functional evidence for this hypothesis has remained incomplete, due to technical difficulties. Here, we show that ectopically expressed Dll induces ectopic elemental color patterns in the adult wings of the blue pansy butterfly, Junonia orithya (Lepidoptera, Nymphalidae). Using baculovirus-mediated gene transfer, we misexpressed Dll protein fused with green fluorescent protein (GFP) in pupal wings, resulting in ectopic color patterns, but not the formation of intact eyespots. Induced changes included clusters of black and orange scales (a basic feature of eyespot patterns), black and gray scales, and inhibition of cover scale development. In contrast, ectopic expression of GFP alone did not induce any color pattern changes using the same baculovirus-mediated gene transfer system. These results suggest that Dll plays an instructive role in the development of color pattern elements in butterfly wings, although Dll alone may not be sufficient to induce a complete eyespot. This study thus experimentally supports the hypothesis of Dll function in eyespot development.

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals

Science.gov (United States)

Zeng, Ying; Yang, Kai; Tong, Li; Yan, Bin

2018-01-01

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods. PMID:29534515

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals.

Science.gov (United States)

Zhuang, Ning; Zeng, Ying; Yang, Kai; Zhang, Chi; Tong, Li; Yan, Bin

2018-03-12

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods.

Halobenzoquinone-Induced Alteration of Gene Expression Associated with Oxidative Stress Signaling Pathways.

Science.gov (United States)

Li, Jinhua; Moe, Birget; Liu, Yanming; Li, Xing-Fang

2018-06-05

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) that effectively induce reactive oxygen species and oxidative damage in vitro. However, the impacts of HBQs on oxidative-stress-related gene expression have not been investigated. In this study, we examined alterations in the expression of 44 genes related to oxidative-stress-induced signaling pathways in human uroepithelial cells (SV-HUC-1) upon exposure to six HBQs. The results show the structure-dependent effects of HBQs on the studied gene expression. After 2 h of exposure, the expression levels of 9 to 28 genes were altered, while after 8 h of exposure, the expression levels of 29 to 31 genes were altered. Four genes ( HMOX1, NQO1, PTGS2, and TXNRD1) were significantly upregulated by all six HBQs at both exposure time points. Ingenuity pathway analysis revealed that the Nrf2 pathway was significantly responsive to HBQ exposure. Other canonical pathways responsive to HBQ exposure included GSH redox reductions, superoxide radical degradation, and xenobiotic metabolism signaling. This study has demonstrated that HBQs significantly alter the gene expression of oxidative-stress-related signaling pathways and contributes to the understanding of HBQ-DBP-associated toxicity.

Changes in gluteal muscle forces with alteration of footstrike pattern during running.

Science.gov (United States)

Vannatta, Charles Nathan; Kernozek, Thomas W; Gheidi, Naghmeh

2017-10-01

Gait retraining is a common form of treatment for running related injuries. Proximal factors at the hip have been postulated as having a role in the development of running related injuries. How altering footstrike affects hip muscles forces and kinematics has not been described. Thus, we aimed to quantify differences in hip muscle forces and hip kinematics that may occur when healthy runners are instructed to alter their foot strike pattern from their habitual rear-foot strike to a forefoot strike. This may gain insight on the potential etiology and treatment methods of running related lower extremity injury. Twenty-five healthy female runners completed a minimum of 10 running trials in a controlled laboratory setting under rear-foot strike and instructed forefoot strike conditions. Kinetic and kinematic data were used in an inverse dynamic based static optimization to estimate individual muscle forces during running. Within subject differences were investigated using a repeated measures multi-variate analysis of variance. Peak gluteus medius and minimus and hamstring forces were reduced while peak gluteus maximus force was increased when running with an instructed forefoot strike pattern. Peak hip adduction, hip internal rotation, and heel-COM distance were also reduced. Therefore, instructing habitual rearfoot strike runners to run with a forefoot strike pattern resulted in changes in peak gluteal and hamstring muscle forces and hip kinematics. These changes may be beneficial to the development and treatment of running related lower extremity injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

Energy Technology Data Exchange (ETDEWEB)

Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2014-02-01

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

International Nuclear Information System (INIS)

Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

2014-01-01

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced

Congenital heart malformations induced by hemodynamic altering surgical interventions

Directory of Open Access Journals (Sweden)

Madeline eMidgett

2014-08-01

Full Text Available Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

Hypoxia‐induced alterations of G2 checkpoint regulators

OpenAIRE

Hasvold, Grete; Lund-Andersen, Christin; Lando, Malin; Patzke, Sebastian; Hauge, Sissel; Suo, ZhenHe; Lyng, Heidi; Syljuåsen, Randi G.

2016-01-01

Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, genome stability is also surveilled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can influence the DNA damage‐induced cell cycle checkpoints. Here, we show that hypoxia (24 h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting o...

Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in wheat.

Science.gov (United States)

Gao, Lihong; Diarso, Moussa; Zhang, Ai; Zhang, Huakun; Dong, Yuzhu; Liu, Lixia; Lv, Zhenling; Liu, Bao

2016-01-01

Aneuploidy causes changes in gene expression and phenotypes in all organisms studied. A previous study in the model plant Arabidopsis thaliana showed that aneuploidy-generated phenotypic changes can be inherited to euploid progenies and implicated an epigenetic underpinning of the heritable variations. Based on an analysis by amplified fragment length polymorphism and methylation-sensitive amplified fragment length polymorphism markers, we found that although genetic changes at the nucleotide sequence level were negligible, extensive changes in cytosine DNA methylation patterns occurred in all studied homeologous group 1 whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with monosomic 1A showing the greatest amount of methylation changes. The changed methylation patterns were inherited by euploid progenies derived from the aneuploid parents. The aneuploidy-induced DNA methylation alterations and their heritability were verified at selected loci by bisulfite sequencing. Our data have provided empirical evidence supporting earlier suggestions that heritability of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A - was able to cause significant epigenetic divergence of the aneuploid plants and their euploid progenies also lends support to recent suggestions that aneuploidy may have played an important and protracted role in polyploid genome evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Altered placental DNA methylation patterns associated with maternal smoking: current perspectives

Directory of Open Access Journals (Sweden)

Maccani JZ

2015-05-01

Full Text Available Jennifer ZJ Maccani, Matthew A Maccani Penn State Tobacco Center of Regulatory Science, College of Medicine, Department of Public Health Sciences, Hershey, PA, USA Abstract: The developmental origins of health and disease hypothesis states that adverse early life exposures can have lasting, detrimental effects on lifelong health. Exposure to maternal cigarette smoking during pregnancy is associated with morbidity and mortality in offspring, including increased risks for miscarriage, stillbirth, low birth weight, preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy interferes with placental growth and functioning, and it has been proposed that this may occur through the disruption of normal and necessary placental epigenetic patterns. Epigenome-wide association studies have identified a number of differentially methylated placental genes that are associated with maternal smoking during pregnancy, including RUNX3, PURA, GTF2H2, GCA, GPR135, and HKR1. The placental methylation status of RUNX3 and NR3C1 has also been linked to adverse infant outcomes, including preterm birth and low birth weight, respectively. Candidate gene analyses have also found maternal smoking-associated placental methylation differences in the NR3C1, CYP1A1, HTR2A, and HSD11B2 genes, as well as in the repetitive elements LINE-1 and AluYb8. The differential methylation patterns of several genes have been confirmed to also exhibit altered gene expression patterns, including CYP1A1, CYP19A1, NR3C1, and HTR2A. Placental methylation patterns associated with maternal smoking during pregnancy may be largely gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is important for future research to investigate the mechanistic roles that these differentially methylated genes may play in mediating the association between maternal smoking during pregnancy and disease in later life, as well

Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

Science.gov (United States)

C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

2014-12-01

3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

Surface and elemental alterations of dental alloys induced by electro discharge machining (EDM).

Science.gov (United States)

Zinelis, Spiros

2007-05-01

To evaluate the surface and elemental alterations induced by electro discharge machining (EDM) on the surface of dental cast alloys used for the fabrication of implant retained meso- and super-structures. A completed cast model of an arch that received dental implants was used for the preparation of six wax patterns which were divided into three groups (Au, Co and Ti). The wax patterns of the Au and Co groups were invested with conventional phosphate-bonded silica-based investment material and the Ti group with magnesia-based investment material. The investment rings of the Au and Co groups were cast with an Au-Ag alloy (Stabilor G) and a Co-Cr base alloy (Okta C), respectively, while the investment rings of group Ti were cast with cp Ti (Biotan). One casting of each group was subjected to electro discharge machining (EDM); the other was conventionally ground and polished. The surface morphology and the elemental compositions of conventionally and EDM-finished surfaces were studied by SEM/X-ray EDS analysis. Six spectra were collected from each surface employing the area scan mode and the mean value of each element between conventionally and EDM-finished surfaces was statistically analyzed by t-test (a=0.05). Then the specimens of each group were cut perpendicular to their longitudinal axis and after metallographic grinding and polishing the cross-sections studied under the SEM. The EDM surfaces showed a significant increase in C due to the decomposition of the dielectric fluid during spark erosion. Moreover, a significant Cu uptake was noted on these surfaces from the decomposition of the Cu electrodes used for EDM. Cross-sectional analysis showed that all alloys developed a superficial zone (recast layer) varying from 2 microm for Au-Ag to 10 microm for Co-Cr alloy. The elemental composition of dental alloy surfaces is significantly altered after EDM treatment.

Are muscle activation patterns altered during shod and barefoot running with a forefoot footfall pattern?

Science.gov (United States)

Ervilha, Ulysses Fernandes; Mochizuki, Luis; Figueira, Aylton; Hamill, Joseph

2017-09-01

This study aimed to investigate the activation of lower limb muscles during barefoot and shod running with forefoot or rearfoot footfall patterns. Nine habitually shod runners were asked to run straight for 20 m at self-selected speed. Ground reaction forces and thigh and shank muscle surface electromyographic (EMG) were recorded. EMG outcomes (EMG intensity [iEMG], latency between muscle activation and ground reaction force, latency between muscle pairs and co-activation index between muscle pairs) were compared across condition (shod and barefoot), running cycle epochs (pre-strike, strike, propulsion) and footfall (rearfoot and forefoot) by ANOVA. Condition affected iEMG at pre-strike epoch. Forefoot and rearfoot strike patterns induced different EMG activation time patterns affecting co-activation index for pairs of thigh and shank muscles. All these timing changes suggest that wearing shoes or not is less important for muscle activation than the way runners strike the foot on the ground. In conclusion, the guidance for changing external forces applied on lower limbs should be pointed to the question of rearfoot or forefoot footfall patterns.

Cold-induced alteration in the global structure of the male sex ...

Indian Academy of Sciences (India)

Cold-induced alteration in the global structure of the male sex ... dar et al. 1978). Chromosome preparated from a single pair of salivary glands show extremely puffy and diffuse ..... Akhtar A. 2003 Dosage compensation: an intertwined world of.

Hyperthermia-induced alteration of yeast susceptibility to mutation

International Nuclear Information System (INIS)

Mitchel, R.E.J.; Morrison, D.P.

1985-01-01

Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

Energy Technology Data Exchange (ETDEWEB)

Tavares, J.G.P. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Universidade Iguaçu, Campos V, Itaperuna, RJ (Brazil); Faculdade de Minas, Muriaé, MG (Brazil); Vasques, E.R. [Departamento de Gastroenterologia, LIM 37, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Arida, R.M. [Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cavalheiro, E.A. [Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cabral, F.R.; Torres, L.B. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Godoy, C.M.G. [Departamento de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Gomes da Silva, S. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Núcleo de Pesquisas Tecnológicas, Programa Integrado em Engenharia Biomédica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP (Brazil)

2015-01-13

The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

International Nuclear Information System (INIS)

Tavares, J.G.P.; Vasques, E.R.; Arida, R.M.; Cavalheiro, E.A.; Cabral, F.R.; Torres, L.B.; Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A.; Godoy, C.M.G.; Gomes da Silva, S.

2015-01-01

The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode

Acupuncture induce the different modulation patterns of the default mode network: an fMRI study

Science.gov (United States)

Liu, Peng; Qin, Wei; Tian, Jie; Zhang, Yi

2009-02-01

According to Traditional Chinese Medicine (TCM) theory and certain clinical treatment reports, the sustained effects of acupuncture indeed exist, which may last several minutes or hours. Furthermore, increased attention has fallen on the sustained effects of acupuncture. Recently, it is reported that the sustained acupuncture effects may alter the default mode network (DMN). It raises interesting questions: whether the modulations of acupuncture effects to the DMN are still detected at other acupoints and whether the modulation patterns are different induced by different acupoints. In the present study, we wanted to investigate the questions. An experiment fMRI design was carried out on 36 subjects with the electroacupuncture stimulation (EAS) at the three acupoints: Guangming (GB37), Kunlun (BL60) and Jiaoxin (KI8) on the left leg. The data sets were analyzed by a data driven method named independent component analysis (ICA). The results indicated that the three acupoints stimulations may modulate the DMN. Moreover, the modulation patterns were distinct. We suggest the different modulation patterns on the DMN may attribute to the distinct functional effects of acupoints.

The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Directory of Open Access Journals (Sweden)

Cristina Rodríguez-Miguel

Full Text Available Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(aanthracene (DMBA-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3 DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

Altered neuronal firing pattern of the basal ganglia nucleus plays a role in levodopa-induced dyskinesia in patients with Parkinson's disease

Directory of Open Access Journals (Sweden)

Xiaoyu eLi

2015-11-01

Full Text Available Background: Levodopa therapy alleviates the symptoms of Parkinson's disease (PD, but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID. Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1±11.0 years; disease duration, 8.7±5.6 years were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr scores ranged from 2 to 4 and their UPDRS III scores were 28.5±5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7±1.6. Microelectrode recording was performed in the globus pallidus internus (GPi and subthalamic nucleus (STN during pallidotomy (n=12 or STN deep brain stimulation (DBS; bilateral, n=12; unilateral, n=6. The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs and the corresponding coefficient of variation (CV. Results: A total of 295 neurons were identified from the GPi (n=12 and STN (n=18. These included 26 (8.8% highly grouped discharge, 30 (10.2% low frequency firing, 78 (26.4% rapid tonic discharge, 103 (34.9% irregular activity, and 58 (19.7% tremor-related activity. There were significant differences between the two groups (P<0.05 for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.

AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination.

Science.gov (United States)

Kobayashi, Maki; Aida, Masatoshi; Nagaoka, Hitoshi; Begum, Nasim A; Kitawaki, Yoko; Nakata, Mikiyo; Stanlie, Andre; Doi, Tomomitsu; Kato, Lucia; Okazaki, Il-mi; Shinkura, Reiko; Muramatsu, Masamichi; Kinoshita, Kazuo; Honjo, Tasuku

2009-12-29

To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the Smu region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage.

Aging induced ER stress alters sleep and sleep homeostasis

Science.gov (United States)

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2014-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

Neural code alterations and abnormal time patterns in Parkinson’s disease

Science.gov (United States)

Andres, Daniela Sabrina; Cerquetti, Daniel; Merello, Marcelo

2015-04-01

Objective. The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson’s disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. Approach. We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. Main results. At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson’s disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. Significance. We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson’s disease.

Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle.

Science.gov (United States)

Li, Yin; Hamilton, Katherine J; Lai, Anne Y; Burns, Katherine A; Li, Leping; Wade, Paul A; Korach, Kenneth S

2014-03-01

Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes. We examined a role for nuclear receptor activity in association with DNA methylation and altered gene expression. We used the neonatal DES exposure mouse model to examine DNA methylation patterns via bisulfite conversion sequencing in SVs of wild-type (WT) and ERα-knockout (αERKO) mice. The DNA methylation status at four specific CpGs (-160, -237, -306, and -367) in the Svs4 gene promoter changed during mouse development from methylated to unmethylated, and DES prevented this change at 10 weeks of age in WT SV. At two specific CpGs (-449 and -459) of the Ltf gene promoter, DES altered the methylation status from methylated to unmethylated. Alterations in DNA methylation of Svs4 and Ltf were not observed in αERKO SVs, suggesting that changes of methylation status at these CpGs are ERα dependent. The methylation status was associated with the level of gene expression. In addition, gene expression of three epigenetic modifiers-DNMT3A, MBD2, and HDAC2-increased in the SV of DES-exposed WT mice. DES-induced hormonal toxicity resulted from altered gene expression of Svs4 and Ltf associated with changes in DNA methylation that were mediated by ERα. Alterations in gene expression of DNMT3A, MBD2, and HDAC2 in DES-exposed male mice may be involved in mediating the changes in methylation status in the SV. Li Y, Hamilton KJ, Lai AY, Burns KA, Li L, Wade PA, Korach KS. 2014. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262-268; http://dx.doi.org/10.1289/ehp.1307351.

Effects of Ascorbic Acid on Garlic-induced Alterations in Semen ...

African Journals Online (AJOL)

Effects of Ascorbic Acid on Garlic-induced Alterations in Semen Parameters Of Wistar Rats. GO Omotoso, IO Onanuga, AAG Jimoh. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/tjhc.v18i2.69616 · AJOL African Journals ...

Sodium cyanide induced alteration in the whole animal oxygen consumption and behavioural pattern of freshwater fish Labeo rohita.

Science.gov (United States)

David, Muniswamy; Sangeetha, Jeyabalan; Harish, Etigemane R

2015-03-01

Sodium cyanide is a common environmental pollutant which is mainly used in many industries such as mining, electroplating, steel manufacturing, pharmaceutical production and other specialized applications including dyes and agricultural products. It enters aquatic environment through effluents from these industries. Static renewal bioassay test has been conducted to determine LC, of sodium cyanide on indigenous freshwater carp, Labeo rohita. The behavioural pattern and oxygen consumption were observed in fish at both lethal and sub lethal concentrations. Labeo rohita in toxic media exhibited irregular and erratic swimming movements, hyper excitability, loss of equilibrium and shrinking to the bottom, which may be due to inhibition of cytochrome C oxidase activity and decreased blood pH. The combination of cytotoxic hypoxia with lactate acidosis depresses the central nervous system resulting in respiratory arrest and death. Decrease in oxygen consumption was observed at both lethal and sub lethal concentrations of sodium cyanide. Mortality was insignificant at sub lethal concentration test when fishes were found under stress. Consequence of impaired oxidative metabolism and elevated physiological response by fish against sodium cyanide stress showed alteration in respiratory rate.

Ubiquitin-dependent system controls radiation induced apoptosis

International Nuclear Information System (INIS)

Delic, J.; Magdelenat, H.; Glaisner, S.; Magdelenat, H.; Maciorowski, Z.

1997-01-01

The selective proteolytic pathway, dependent upon 'N-end rule' protein recognition/ubiquitination and on the subsequent proteasome dependent processing of ubiquitin conjugates, operates in apoptosis induced by γ-irradiation. The proteasome inhibitor peptide aldehyde, MG132, efficiently induced apoptosis and was also able (at doses lower than those required for apoptosis induction) to potentiate apoptosis induced by DNA damage. Its specificity is suggested by the induction of the ubiquitin (UbB and UbC) and E1 (ubiquitin activating enzyme) genes and by an altered ubiquitination pattern. More selectively, a di-peptide competitor of the 'N-end rule' of ubiquitin dependent protein processing inhibited radiation induced apoptosis. This inhibition is also followed by an altered ubiquitination pattern and by activation of Poly (ADP-ribose) polymerase (PARP). These data strongly suggest that early apoptosis radiation induced events are controlled by ubiquitin-dependent proteolytic processing. (author)

Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

Science.gov (United States)

Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

2013-01-01

Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

Directory of Open Access Journals (Sweden)

Philip Klepeisz

Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

Exercise Alters Gait Pattern but Not Knee Load in Patients with Knee Osteoarthritis

Directory of Open Access Journals (Sweden)

Ssu-Yu Chang

2016-01-01

Full Text Available Six female patients with bilateral medial knee OA and 6 healthy controls were recruited. Patients with knee OA received a 6-week physiotherapist-supervised and home-based exercise program. Outcome measures, including the Western Ontario and McMaster Universities Arthritis Index and Short Form-36 Health Survey as well as objective biomechanical indices were obtained at baseline and follow-up. After treatment, no significant difference was observed in the knee abductor moment (KAM, lever arm, and ground reaction force. We, however, observed significantly improved pain and physical function as well as altered gait patterns, including a higher hip flexor moment and hip extension angle with a faster walking speed. Although KAM was unchanged, patients with bilateral knee OA showed an improved walking speed and altered the gait pattern after 6 weeks of supervised exercise. This finding suggests that the exercise intervention improves proximal joint mechanics during walking and can be considered for patients with bilateral knee OA. Non-weight-bearing strengthening without external resistance combined with stretching exercise may be an option to improve pain and function in individuals with OA who cannot perform high resistance exercises owing to pain or other reasons.

Altered brain network modules induce helplessness in major depressive disorder.

Science.gov (United States)

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

2014-10-01

The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

Climate change induced rainfall patterns affect wheat productivity and agroecosystem functioning dependent on soil types

Science.gov (United States)

Tabi Tataw, James; Baier, Fabian; Krottenthaler, Florian; Pachler, Bernadette; Schwaiger, Elisabeth; Whylidal, Stefan; Formayer, Herbert; Hösch, Johannes; Baumgarten, Andreas; Zaller, Johann G.

2014-05-01

Wheat is a crop of global importance supplying more than half of the world's population with carbohydrates. We examined, whether climate change induced rainfall patterns towards less frequent but heavier events alter wheat agroecosystem productivity and functioning under three different soil types. Therefore, in a full-factorial experiment Triticum aestivum L. was cultivated in 3 m2 lysimeter plots containing the soil types sandy calcaric phaeozem, gleyic phaeozem or calcic chernozem. Prognosticated rainfall patterns based on regionalised climate change model calculations were compared with current long-term rainfall patterns; each treatment combination was replicated three times. Future rainfall patterns significantly reduced wheat growth and yield, reduced the leaf area index, accelerated crop development, reduced arbuscular mycorrhizal fungi colonisation of roots, increased weed density and the stable carbon isotope signature (δ13C) of both old and young wheat leaves. Different soil types affected wheat growth and yield, ecosystem root production as well as weed abundance and biomass. The interaction between climate and soil type was significant only for the harvest index. Our results suggest that even slight changes in rainfall patterns can significantly affect the functioning of wheat agroecosystems. These rainfall effects seemed to be little influenced by soil types suggesting more general impacts of climate change across different soil types. Wheat production under future conditions will likely become more challenging as further concurrent climate change factors become prevalent.

Patellofemoral joint stress during running with alterations in foot strike pattern.

Science.gov (United States)

Vannatta, Charles Nathan; Kernozek, Thomas W

2015-05-01

This study aimed to quantify differences in patellofemoral joint stress that may occur when healthy runners alter their foot strike pattern from their habitual rearfoot strike to a forefoot strike to gain insight on the potential etiology and treatment methods of patellofemoral pain. Sixteen healthy female runners completed 20 running trials in a controlled laboratory setting under rearfoot strike and forefoot strike conditions. Kinetic and kinematic data were used to drive a static optimization technique to estimate individual muscle forces to input into a model of the patellofemoral joint to estimate joint stress during running. Peak patellofemoral joint stress and the stress-time integral over stance phase decreased by 27% and 12%, respectively, in the forefoot strike condition (P forefoot strike condition (P forefoot strike (P forefoot strike condition (P strike pattern to a forefoot strike results in consistent reductions in patellofemoral joint stress independent of changes in step length. Thus, implementation of forefoot strike training programs may be warranted in the treatment of runners with patellofemoral pain. However, it is suggested that the transition to a forefoot strike pattern should be completed in a graduated manner.

Time course of ozone-induced changes in breathing pattern in healthy exercising humans.

Science.gov (United States)

Schelegle, Edward S; Walby, William F; Adams, William C

2007-02-01

We examined the time course of O3-induced changes in breathing pattern in 97 healthy human subjects (70 men and 27 women). One- to five-minute averages of breathing frequency (f(B)) and minute ventilation (Ve) were used to generate plots of cumulative breaths and cumulative exposure volume vs. time and cumulative exposure volume vs. cumulative breaths. Analysis revealed a three-phase response; delay, no response detected; onset, f(B) began to increase; response, f(B) stabilized. Regression analysis was used to identify four parameters: time to onset, number of breaths at onset, cumulative inhaled dose of ozone at onset of O3-induced tachypnea, and the percent change in f(B). The effect of altering O3 concentration, Ve, atropine treatment, and indomethacin treatment were examined. We found that the lower the O3 concentration, the greater the number of breaths at onset of tachypnea at a fixed ventilation, whereas number of breaths at onset of tachypnea remains unchanged when Ve is altered and O3 concentration is fixed. The cumulative inhaled dose of O3 at onset of tachypnea remained constant and showed no relationship with the magnitude of percent change in f(B). Atropine did not affect any of the derived parameters, whereas indomethacin did not affect time to onset, number of breaths at onset, or cumulative inhaled dose of O3 at onset of tachypnea but did attenuate percent change in f(B). The results are discussed in the context of dose response and intrinsic mechanisms of action.

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

Directory of Open Access Journals (Sweden)

Shuhua Xiao

2002-07-01

Full Text Available Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

International Nuclear Information System (INIS)

Tong, Ying; Smith, M.A.; Tucker, S.B.

1997-01-01

Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

Magnetoresistance and ion bombardment induced magnetic patterning

International Nuclear Information System (INIS)

Hoeink, V.

2008-01-01

In this thesis the combination of the magnetic patterning of the unidirectional anisotropy and the tunnel magnetoresistance effect is investigated. In my diploma thesis, it has been shown that it is in principle possible to use the magnetic patterning by ion bombardment to magnetically structure the pinned layer in magnetic tunnel junctions (MTJs) with alumina barrier. Furthermore, it has been shown that the side effects which have been observed after this treatment can be at least reduced by an additional heating step. Starting from this point, the applicability of ion bombardment induced magnetic patterning (IBMP) in general and the combination of IBMP and MTJs in particular is investigated and new applications are developed. (orig.)

Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton alteration.

Science.gov (United States)

Lee, Su Jin; Park, Jeen Woo; Kang, Beom Sik; Lee, Dong-Seok; Lee, Hyun-Shik; Choi, Sooyoung; Kwon, Oh-Shin

2017-06-01

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and 14-3-3ζ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to 14-3-3ζ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling. [BMB Reports 2017; 50(6): 335-340].

Individualized prediction of schizophrenia based on the whole-brain pattern of altered white matter tract integrity.

Science.gov (United States)

Chen, Yu-Jen; Liu, Chih-Min; Hsu, Yung-Chin; Lo, Yu-Chun; Hwang, Tzung-Jeng; Hwu, Hai-Gwo; Lin, Yi-Tin; Tseng, Wen-Yih Isaac

2018-01-01

A schizophrenia diagnosis relies on characteristic symptoms identified by trained physicians, and is thus prone to subjectivity. This study developed a procedure for the individualized prediction of schizophrenia based on whole-brain patterns of altered white matter tract integrity. The study comprised training (108 patients and 144 controls) and testing (60 patients and 60 controls) groups. Male and female participants were comparable in each group and were analyzed separately. All participants underwent diffusion spectrum imaging of the head, and the data were analyzed using the tract-based automatic analysis method to generate a standardized two-dimensional array of white matter tract integrity, called the connectogram. Unique patterns in the connectogram that most accurately identified schizophrenia were systematically reviewed in the training group. Then, the diagnostic performance of the patterns was individually verified in the testing group by using receiver-operating characteristic curve analysis. The performance was high in men (accuracy = 0.85) and satisfactory in women (accuracy = 0.75). In men, the pattern was located in discrete fiber tracts, as has been consistently reported in the literature; by contrast, the pattern was widespread over all tracts in women. These distinct patterns suggest that there is a higher variability in the microstructural alterations in female patients than in male patients. The individualized prediction of schizophrenia is feasible based on the different whole-brain patterns of tract integrity. The optimal masks and their corresponding regions in the fiber tracts could serve as potential imaging biomarkers for schizophrenia. Hum Brain Mapp 39:575-587, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evidence of an evolutionary hourglass pattern in herbivory-induced transcriptomic responses.

Science.gov (United States)

Durrant, Matthew; Boyer, Justin; Zhou, Wenwu; Baldwin, Ian T; Xu, Shuqing

2017-08-01

Herbivory-induced defenses are specific and activated in plants when elicitors, frequently found in the herbivores' oral secretions, are introduced into wounds during attack. While complex signaling cascades are known to be involved, it remains largely unclear how natural selection has shaped the evolution of these induced defenses. We analyzed herbivory-induced transcriptomic responses in wild tobacco, Nicotiana attenuata, using a phylotranscriptomic approach that measures the origin and sequence divergence of herbivory-induced genes. Highly conserved and evolutionarily ancient genes of primary metabolism were activated at intermediate time points (2-6 h) after elicitation, while less constrained and young genes associated with defense signaling and biosynthesis of specialized metabolites were activated at early (before 2 h) and late (after 6 h) stages of the induced response, respectively - a pattern resembling the evolutionary hourglass pattern observed during embryogenesis in animals and the developmental process in plants and fungi. The hourglass patterns found in herbivory-induced defense responses and developmental process are both likely to be a result of signaling modularization and differential evolutionary constraints on the modules involved in the signaling cascade. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

Science.gov (United States)

Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (phypopituitaric patients. In particular, triglycerides (phypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Changes in foot and shank coupling due to alterations in foot strike pattern during running.

Science.gov (United States)

Pohl, Michael B; Buckley, John G

2008-03-01

Determining if and how the kinematic relationship between adjacent body segments changes when an individual's gait pattern is experimentally manipulated can yield insight into the robustness of the kinematic coupling across the associated joint(s). The aim of this study was to assess the effects on the kinematic coupling between the forefoot, rearfoot and shank during ground contact of running with alteration in foot strike pattern. Twelve subjects ran over-ground using three different foot strike patterns (heel strike, forefoot strike, toe running). Kinematic data were collected of the forefoot, rearfoot and shank, which were modelled as rigid segments. Coupling at the ankle-complex and midfoot joints was assessed using cross-correlation and vector coding techniques. In general good coupling was found between rearfoot frontal plane motion and transverse plane shank rotation regardless of foot strike pattern. Forefoot motion was also strongly coupled with rearfoot frontal plane motion. Subtle differences were noted in the amount of rearfoot eversion transferred into shank internal rotation in the first 10-15% of stance during heel strike running compared to forefoot and toe running, and this was accompanied by small alterations in forefoot kinematics. These findings indicate that during ground contact in running there is strong coupling between the rearfoot and shank via the action of the joints in the ankle-complex. In addition, there was good coupling of both sagittal and transverse plane forefoot with rearfoot frontal plane motion via the action of the midfoot joints.

Boundary-induced pattern formation from uniform temporal oscillation

Science.gov (United States)

Kohsokabe, Takahiro; Kaneko, Kunihiko

2018-04-01

Pattern dynamics triggered by fixing a boundary is investigated. By considering a reaction-diffusion equation that has a unique spatially uniform and limit cycle attractor under a periodic or Neumann boundary condition, and then by choosing a fixed boundary condition, we found three novel phases depending on the ratio of diffusion constants of activator to inhibitor: transformation of temporally periodic oscillation into a spatially periodic fixed pattern, travelling wave emitted from the boundary, and aperiodic spatiotemporal dynamics. The transformation into a fixed, periodic pattern is analyzed by crossing of local nullclines at each spatial point, shifted by diffusion terms, as is analyzed by using recursive equations, to obtain the spatial pattern as an attractor. The generality of the boundary-induced pattern formation as well as its relevance to biological morphogenesis is discussed.

Subcellular distribution of swine vesicular disease virus proteins and alterations induced in infected cells: A comparative study with foot-and-mouth disease virus and vesicular stomatitis virus

International Nuclear Information System (INIS)

Martin-Acebes, Miguel A.; Gonzalez-Magaldi, Monica; Rosas, Maria F.; Borrego, Belen; Brocchi, Emiliana; Armas-Portela, Rosario; Sobrino, Francisco

2008-01-01

The intracellular distribution of swine vesicular disease virus (SVDV) proteins and the induced reorganization of endomembranes in IBRS-2 cells were analyzed. Fluorescence to new SVDV capsids appeared first upon infection, concentrated in perinuclear circular structures and colocalized to dsRNA. As in foot-and-mouth disease virus (FMDV)-infected cells, a vesicular pattern was predominantly found in later stages of SVDV capsid morphogenesis that colocalized with those of non-structural proteins 2C, 2BC and 3A. These results suggest that assembly of capsid proteins is associated to the replication complex. Confocal microscopy showed a decreased fluorescence to ER markers (calreticulin and protein disulfide isomerase), and disorganization of cis-Golgi gp74 and trans-Golgi caveolin-1 markers in SVDV- and FMDV-, but not in vesicular stomatitis virus (VSV)-infected cells. Electron microscopy of SVDV-infected cells at an early stage of infection revealed fragmented ER cisternae with expanded lumen and accumulation of large Golgi vesicles, suggesting alterations of vesicle traffic through Golgi compartments. At this early stage, FMDV induced different patterns of ER fragmentation and Golgi alterations. At later stages of SVDV cytopathology, cells showed a completely vacuolated cytoplasm containing vesicles of different sizes. Cell treatment with brefeldin A, which disrupts the Golgi complex, reduced SVDV (∼ 5 log) and VSV (∼ 4 log) titers, but did not affect FMDV growth. Thus, three viruses, which share target tissues and clinical signs in natural hosts, induce different intracellular effects in cultured cells

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

Science.gov (United States)

Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

2014-06-01

Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

Patterns of experimentally induced pain in pericranial muscles

DEFF Research Database (Denmark)

Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

2006-01-01

into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

Mitomycin C induced alterations in antioxidant enzyme levels in a model insect species, Spodoptera eridania.

Science.gov (United States)

Batcabe, J P; MacGill, R S; Zaman, K; Ahmad, S; Pardini, R S

1994-05-01

1. An insect species, the southern armyworm Spodoptera eridania, was used as an in vivo model to examine mitomycin C's (MMC) pro-oxidant effect reflected in alterations of antioxidant enzymes. 2. Following a 2-day exposure to 0.01 and 0.05% w/w dietary concentrations, MMC only induced superoxide dismutase activity. All other enzyme activities were not affected, indicating oxidative stress was mild. 3. Following a 5-day exposure to 0.05% w/w dietary MMC, the activities of superoxide dismutase, glutathione-S-transferase and its peroxidase activity and DT-diaphorase were induced. GR activity was not altered. The high constitutive catalase activity was also not affected. These responses of S. eridania's antioxidant enzymes are analogous to those of mammalian systems in alleviating MMC-induced oxidative stress. 4. S. eridania emerges as an appropriate non-mammalian model for initial and cost-effective screening of drug-induced oxidative stress.

Profiling of altered metabolomic states in Nicotiana tabacum cells induced by priming agents

CSIR Research Space (South Africa)

Mhlongo, MI

2016-10-01

Full Text Available tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones—abscisic acid, methyljasmonate, and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid...

Prevention of shockwave induced functional and morphological alterations: an overview.

Science.gov (United States)

Sarica, Kemal; Yencilek, Faruk

2008-03-01

Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

Patterns induced by magnetic impurities in d-wave superconductors

International Nuclear Information System (INIS)

Zuo Xianjun; Gong Changde; Zhou Yuan

2010-01-01

We investigate the modulated patterns induced by magnetic impurities in d-wave superconductors (DSCs) near optimal doping based on the t-t ' -U-V model. Modulated checkerboard patterns with periodicity of eight or four lattice constants (8a or 4a) in the spin-, charge- and DSC orders are observed. Moreover, the checkerboard modulation in the spin order appear to be robust against parameter changes, which is consistent with neutron-scattering experiments. For the two-impurity case, a modulated stripe-like spin order with periodicity 8a is induced, which coexists with the DSC order. Further experiments of magnetic impurity substitution in DSCs are expected to check these results.

Patterns induced by magnetic impurities in d-wave superconductors

Science.gov (United States)

Zuo, Xian-Jun; Gong, Chang-De; Zhou, Yuan

2010-07-01

We investigate the modulated patterns induced by magnetic impurities in d-wave superconductors (DSCs) near optimal doping based on the t-t-U-V model. Modulated checkerboard patterns with periodicity of eight or four lattice constants (8 a or 4 a) in the spin-, charge- and DSC orders are observed. Moreover, the checkerboard modulation in the spin order appear to be robust against parameter changes, which is consistent with neutron-scattering experiments. For the two-impurity case, a modulated stripe-like spin order with periodicity 8 a is induced, which coexists with the DSC order. Further experiments of magnetic impurity substitution in DSCs are expected to check these results.

High-Altitude-Induced alterations in Gut-Immune Axis: A review.

Science.gov (United States)

Khanna, Kunjan; Mishra, K P; Ganju, Lilly; Kumar, Bhuvnesh; Singh, Shashi Bala

2018-03-04

High-altitude sojourn above 8000 ft is increasing day by day either for pilgrimage, mountaineering, holidaying or for strategic reasons. In India, soldiers are deployed to these high mountains for their duty or pilgrims visit to the holy places, which are located at very high altitude. A large population also resides permanently in high altitude regions. Every year thousands of pilgrims visit Holy cave of Shri Amarnath ji, which is above 15 000 ft. The poor acclimatization to high altitude may cause alteration in immunity. The low oxygen partial pressure may cause alterations in gut microbiota, which may cause changes in gut immunity. Effect of high altitude on gut-associated mucosal system is new area of research. Many studies have been carried out to understand the physiology and immunology behind the high-altitude-induced gut problems. Few interventions have also been discovered to circumvent the problems caused due to high-altitude conditions. In this review, we have discussed the effects of high-altitude-induced changes in gut immunity particularly peyer's patches, NK cells and inflammatory cytokines, secretary immunoglobulins and gut microbiota. The published articles from PubMed and Google scholar from year 1975 to 2017 on high-altitude hypoxia and gut immunity are cited in this review.

Metabolic and vascular pattern in medial pterygoid muscle is altered by chronic stress in an animal model of hypodontia.

Science.gov (United States)

Fernández, Rodrigo Alberto Restrepo; Pereira, Yamba Carla Lara; Iyomasa, Daniela Mizusaki; Calzzani, Ricardo Alexandre; Leite-Panissi, Christie Ramos Andrade; Iyomasa, Mamie Mizusaki; Nascimento, Glauce Crivelaro

2018-03-01

Psychological stress is an important perpetuating, worsening and risk factor for temporomandibular disorders of muscular or articular origin. Occlusion instability, by the way, is considered a risk factor of this pathology and can be reproduced in some experimental animal models. The exact physiologic mechanism underlying these relations however, remains unclear. Our purpose was to test the hypothesis that chronic stress and unilateral exodontia induce metabolic and vascular changes in the medial pterygoid muscle of rats. Adult Wistar rats were submitted to chronic unpredictable stress and/or unilateral exodontia and their plasma and medial pterygoid muscle were removed for analysis. The parameters evaluated included plasma levels of corticosterone, metabolic activity by succinate dehydrogenase, oxidative capacity by nicotinamide adenine dinucleotide diaphorase, capillary density by laminin and alfa-CD staining and reactive oxidative species production. Chronic unpredictable stress as an isolated factor, increased oxidative metabolism, capillary density and reactive oxygen species production at medial pterygoid muscle. Conversely, exodontia has a main effect in metabolism, promoting glycolytic transformation of muscle fibers. Association of both factors induced a major glycolytic pattern in muscle and vascular changes. Our findings provide insights into the mechanisms, possibly inducing metabolic and vascular alterations on medial pterygoid muscle of rats, by which chronic stress and occlusal instabilities might be involved as risk factors in the pathophysiology of temporomandibular disorders with muscular components. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

Directory of Open Access Journals (Sweden)

Roberto G. Pozner

2013-01-01

Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding.

Science.gov (United States)

Gotthardt, Juliet D; Bello, Nicholas T

2017-05-15

Alternate day, intermittent fasting (IMF) can be an effective weight loss strategy. However, the effects of IMF on eating behaviors are not well characterized. We investigated the acute and residual effects of IMF for weight loss on meal patterns in adult obese male C57BL/6 mice. After 8weeks of ad libitum high-fat diet to induce diet-induced obesity (DIO), mice were either continued on ad libitum high-fat diet (HFD) or placed on one of 5 diet strategies for weight loss: IMF of high-fat diet (IMF-HFD), pair-fed to IMF-HFD group (PF-HFD), ad libitum low-fat diet (LFD), IMF of low-fat diet (IMF-LFD), or pair-fed to IMF-LFD group (PF-LFD). After the 4-week diet period, all groups were refed the high-fat diet for 6weeks. By the end of the diet period, all 5 groups had lost weight compared with HFD group, but after 6weeks of HFD re-feeding all groups had similar body weights. On (Day 2) of the diet period, IMF-HFD had greater first meal size and faster eating rate compared with HFD. Also, first meal duration was greater in LFD and IMF-LFD compared with HFD. At the end of the diet period (Day 28), the intermittent fasting groups (IMF-HFD and IMF-LFD) had greater first meal sizes and faster first meal eating rate compared with their respective ad libitum fed groups on similar diets (HFD and LFD). Also, average meal duration was longer on Day 28 in the low-fat diet groups (LFD and IMF-LFD) compared with high-fat diet groups (HFD and IMF-HFD). After 6weeks of HFD re-feeding (Day 70), there were no differences in meal patterns in groups that had previously experienced intermittent fasting compared with ad libitum fed groups. These findings suggest that meal patterns are only transiently altered during alternate day intermittent fasting for weight loss in obese male mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Emersion induces nitrogen release and alteration of nitrogen metabolism in the intertidal genus Porphyra.

Directory of Open Access Journals (Sweden)

Jang K Kim

Full Text Available We investigated emersion-induced nitrogen (N release from Porphyra umbilicalis Kütz. Thallus N concentration decreased during 4 h of emersion. Tissue N and soluble protein contents of P. umbilicalis were positively correlated and decreased during emersion. Growth of P. umbilicalis did not simply dilute the pre-emersion tissue N concentration. Rather, N was lost from tissues during emersion. We hypothesize that emersion-induced N release occurs when proteins are catabolized. While the δ(15N value of tissues exposed to emersion was higher than that of continuously submerged tissues, further discrimination of stable N isotopes did not occur during the 4 h emersion. We conclude that N release from Porphyra during emersion did not result from bacterial denitrification, but possibly as a consequence of photorespiration. The release of N by P. umbilicalis into the environment during emersion suggests a novel role of intertidal seaweeds in the global N cycle. Emersion also altered the physiological function (nitrate uptake, nitrate reductase and glutamine synthetase activity, growth rate of P. umbilicalis and the co-occurring upper intertidal species P. linearis Grev., though in a seasonally influenced manner. Individuals of the year round perennial species P. umbilicalis were more tolerant of emersion than ephemeral, cold temperate P. linearis in early winter. However, the mid-winter populations of both P. linearis and P. umbilicalis, had similar temporal physiological patterns during emersion.

One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits.

Directory of Open Access Journals (Sweden)

Po-Tsun Chen

Full Text Available Most trigger digit (TD patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.

One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits.

Science.gov (United States)

Chen, Po-Tsun; Lin, Chien-Ju; Jou, I-Ming; Chieh, Hsiao-Feng; Su, Fong-Chin; Kuo, Li-Chieh

2013-01-01

Most trigger digit (TD) patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

Directory of Open Access Journals (Sweden)

Magdalena Cristóbal-García

2015-01-01

Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

Histological and Physiological Alterations Induced by Thermal Neutron Fluxes in Male Swiss Albino Mice

International Nuclear Information System (INIS)

Alzergy, A.A.; Emara, N.M.; Abd El-Latif, A.A.; El-Saady, S.M.M.; Emara, N.M.; Abd El-Latif, A.A.

2010-01-01

This work was performed to investigate the biological effects of different thermal neutron fluxes (0.27x10 8 , 0.52X10 8 , 1.089X10 8 , 2.16X10 8 and 4.32X10 8 ) on liver and kidney of male mice using neutron irradiation cell with Ra-Be(α,n) 3 mCi neutron source Leybold (55930). Exposed to various fluxes of thermal neutron induced a dramatic alterations in hepatic and renal functions as indicated by biochemical estimation of several parameters (bilirubin, SGT, and alkaline phosphate .Urea , total protein, and albumin) and confirmed by histological examinations Thermal neutron exposure induces marked increase in the serum activities of total bilirubin, alanine amino transaminase (ALT or GPT), and alkaline phosphate, whereas, urea, total protein and albumin showed marked decline as compared to control group. The physiological changes induced in thermal neutron fluxes dependent manner. Histopathological results revealed mild to severe type of necrosis, and degenerative changes in liver and kidney of male mice exposed to thermal neutron fluxes. Also it was found that the histopathological alterations induced in thermal neutron fluxes dependent manner. It was found that exposed to thermal neutron fluxes irradiation plays prominent role in the development of the physiological alterations in male Swiss albino mice. The Former up normalities as a result of the sequence events followed interaction of radiation with the former biological mater (liver and kidney) of male Swiss albino mice, which are, physical, physicochemical, chemical, and biological stages.

Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

Science.gov (United States)

Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

2017-01-01

Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats.

Science.gov (United States)

Saad, Ramadan A; Mahmoud, Yomna I

2014-12-01

Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bile duct ligation. Bile duct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Game-induced fatigue patterns in elite female soccer

DEFF Research Database (Denmark)

Krustrup, Peter; Zebis, Mette; Jensen, Jack Majgaard

2010-01-01

.06 +/- 0.06 seconds after the game, which was 4% slower (p game-induced effect was observed on vertical jump performance. Significant inverse correlations were observed between Yo-Yo IE2 test performance and fatigue index during the repeated sprint test both......Krustrup, P, Zebis, M, Jensen, JM, and Mohr, M. Game-induced fatigue patterns in elite female soccer. J Strength Cond Res 24(2): 437-441, 2010-The purpose was to examine the fatigue pattern of elite female soccer players after competitive games. Soccer players (n = 23) from the Danish women Premier...... League performed a countermovement vertical jump test, a repeated 30-m sprint test, and the Yo-Yo intermittent endurance level 2 (Yo-Yo IE2) test at rested state and after a competitive game. Average heart rate during the game was 86 +/- 1% of maximal heart rate with no differences between halves. Blood...

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

Science.gov (United States)

Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

2018-02-20

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

Science.gov (United States)

Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

2013-05-05

Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

Directory of Open Access Journals (Sweden)

Mankgopo Magdeline Kgatle

2017-01-01

Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

International Nuclear Information System (INIS)

Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

2011-01-01

Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

Localization of pellicle-induced open contacts using Charge-Induced Voltage Alteration

Energy Technology Data Exchange (ETDEWEB)

Cole, E.I. Jr.; Soden, J.M.

1993-08-01

The recently developed Charge-Induced Voltage Alteration (CIVA) technique for localizing open metal conductors was used successfully to identify transistors with electrically open metal-1 contacts to silicon. The transistors were in the I/O port circuitry of a failing microcontroller and were completely covered by a metal-2 power bus. The root cause of the open contacts was a subtle scratch in the pellicle over the contact reticle. The scratch prevented full exposure of the photoresist, resulting in incomplete removal of the interlevel oxide in several contact windows. In addition to this powerful new application of CIVA, a number of failure analysis techniques utilizing both the electrical and physical properties of the failing microcontrollers were employed to identify and confirm the open contacts. These techniques are reviewed and recommendations are given for improved pellicle/reticle inspection.

Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-02-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

Science.gov (United States)

Michopoulos, Vasiliki

2016-11-01

The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

Transformations of visual memory induced by implied motions of pattern elements.

Science.gov (United States)

Finke, R A; Freyd, J J

1985-10-01

Four experiments measured distortions in short-term visual memory induced by displays depicting independent translations of the elements of a pattern. In each experiment, observers saw a sequence of 4 dot patterns and were instructed to remember the third pattern and to compare it with the fourth. The first three patterns depicted translations of the dots in consistent, but separate directions. Error rates and reaction times for rejecting the fourth pattern as different from the third were substantially higher when the dots in that pattern were displaced slightly forward, in the same directions as the implied motions, compared with when the dots were displaced in the opposite, backward directions. These effects showed little variation across interstimulus intervals ranging from 250 to 2,000 ms, and did not depend on whether the displays gave rise to visual apparent motion. However, they were eliminated when the dots in the fourth pattern were displaced by larger amounts in each direction, corresponding to the dot positions in the next and previous patterns in the same inducing sequence. These findings extend our initial report of the phenomenon of "representational momentum" (Freyd & Finke, 1984a), and help to rule out alternatives to the proposal that visual memories tend to undergo, at least to some extent, the transformations implied by a prior sequence of observed events.

Do Aphids Alter Leaf Surface Temperature Patterns During Early Infestation?

Directory of Open Access Journals (Sweden)

Thomas Cahon

2018-03-01

Full Text Available Arthropods at the surface of plants live in particular microclimatic conditions that can differ from atmospheric conditions. The temperature of plant leaves can deviate from air temperature, and leaf temperature influences the eco-physiology of small insects. The activity of insects feeding on leaf tissues, may, however, induce changes in leaf surface temperatures, but this effect was only rarely demonstrated. Using thermography analysis of leaf surfaces under controlled environmental conditions, we quantified the impact of presence of apple green aphids on the temperature distribution of apple leaves during early infestation. Aphids induced a slight change in leaf surface temperature patterns after only three days of infestation, mostly due to the effect of aphids on the maximal temperature that can be found at the leaf surface. Aphids may induce stomatal closure, leading to a lower transpiration rate. This effect was local since aphids modified the configuration of the temperature distribution over leaf surfaces. Aphids were positioned at temperatures near the maximal leaf surface temperatures, thus potentially experiencing the thermal changes. The feedback effect of feeding activity by insects on their host plant can be important and should be quantified to better predict the response of phytophagous insects to environmental changes.

More consistently altered connectivity patterns for cerebellum and medial temporal lobes than for amygdala and striatum in schizophrenia

Directory of Open Access Journals (Sweden)

Henning ePeters

2016-02-01

Full Text Available Background: Brain architecture can be divided into a cortico-thalamic system and modulatory ‘subcortical-cerebellar’ systems containing key structures such as striatum, medial temporal lobes (MTLs, amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems’ connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems’ connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI. Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems’ activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs (i.e., striatum, MTL, amygdala, cerebellum. Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices (i.e. connectivity between NW and ROIs (allROIs-NW, separateROI-NW, only NWs (NWs-NWs, and only ROIs (allROIs-allROIs as main outcome measures, which were classified by support-vector-machine-based leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56% and 74%, respectively. Considering separate

High salt diet induces metabolic alterations in multiple biological processes of Dahl salt-sensitive rats.

Science.gov (United States)

Wang, Yanjun; Liu, Xiangyang; Zhang, Chen; Wang, Zhengjun

2018-06-01

High salt induced renal disease is a condition resulting from the interactions of genetic and dietary factors causing multiple complications. To understand the metabolic alterations associated with renal disease, we comprehensively analyzed the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS) rats using GC-MS technology and biochemical analyses. Physiological features, serum chemistry, and histopathological data were obtained as complementary information. Our results showed that high salt (HS) intake for 16 weeks caused significant metabolic alterations in both the renal medulla and cortex involving a variety pathways involved in the metabolism of organic acids, amino acids, fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up-regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP + , NADPH oxidase activity and ROS production, suggesting that increased oxidative stress was associated with an altered PPP pathway. The metabolic pathways identified may serve as potential targets for the treatment of renal damage. Our findings provide comprehensive biochemical details about the metabolic responses to a high salt diet, which may contribute to the understanding of renal disease and salt-induced hypertension in SS rats. Copyright © 2018. Published by Elsevier Inc.

Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

Science.gov (United States)

Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

2012-07-01

The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

Using visual feedback distortion to alter coordinated pinching patterns for robotic rehabilitation

Directory of Open Access Journals (Sweden)

Brewer Bambi R

2007-05-01

Full Text Available Abstract Background It is common for individuals with chronic disabilities to continue using the compensatory movement coordination due to entrenched habits, increased perception of task difficulty, or personality variables such as low self-efficacy or a fear of failure. Following our previous work using feedback distortion in a virtual rehabilitation environment to increase strength and range of motion, we address the use of visual feedback distortion environment to alter movement coordination patterns. Methods Fifty-one able-bodied subjects participated in the study. During the experiment, each subject learned to move their index finger and thumb in a particular target pattern while receiving visual feedback. Visual distortion was implemented as a magnification of the error between the thumb and/or index finger position and the desired position. The error reduction profile and the effect of distortion were analyzed by comparing the mean total absolute error and a normalized error that measured performance improvement for each subject as a proportion of the baseline error. Results The results of the study showed that (1 different coordination pattern could be trained with visual feedback and have the new pattern transferred to trials without visual feedback, (2 distorting individual finger at a time allowed different error reduction profile from the controls, and (3 overall learning was not sped up by distorting individual fingers. Conclusion It is important that robotic rehabilitation incorporates multi-limb or finger coordination tasks that are important for activities of daily life in the near future. This study marks the first investigation on multi-finger coordination tasks under visual feedback manipulation.

REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

Directory of Open Access Journals (Sweden)

Nirupama R.

2010-09-01

Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

Analysis of unstable chromosome alterations frequency induced by neutron-gamma mixed field radiation

Energy Technology Data Exchange (ETDEWEB)

Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Vale, Carlos H.F.P.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)], e-mail: psouza@cnen.gov.br, e-mail: jodinilson@cnen.gov.br; Calixto, Merilane S.; Santos, Neide [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica

2009-07-01

Nowadays monitoring chromosome alterations in peripheral blood lymphocytes have been used to access the radiation absorbed dose in individuals exposed accidental or occupationally to gamma radiation. However there are not many studies based on the effects of mixed field neutron-gamma. The radiobiology of neutrons has great importance because in nuclear factories worldwide there are several hundred thousand individuals monitored as potentially receiving doses of neutron. In this paper it was observed the frequencies of unstable chromosome alterations induced by a gamma-neutron mixed field. Blood was obtained from one healthy donor and exposed to mixed field neutron-gamma sources {sup 241}AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphases were analyzed for the presence of chromosome alterations by two experienced scorers. The results suggest that there is the possibility of a directly proportional relationship between absorbed dose of neutron-gamma mixed field radiation and the frequency of unstable chromosome alterations analyzed in this paper. (author)

Analysis of unstable chromosome alterations frequency induced by neutron-gamma mixed field radiation

International Nuclear Information System (INIS)

Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Vale, Carlos H.F.P.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide

2009-01-01

Nowadays monitoring chromosome alterations in peripheral blood lymphocytes have been used to access the radiation absorbed dose in individuals exposed accidental or occupationally to gamma radiation. However there are not many studies based on the effects of mixed field neutron-gamma. The radiobiology of neutrons has great importance because in nuclear factories worldwide there are several hundred thousand individuals monitored as potentially receiving doses of neutron. In this paper it was observed the frequencies of unstable chromosome alterations induced by a gamma-neutron mixed field. Blood was obtained from one healthy donor and exposed to mixed field neutron-gamma sources 241 AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphases were analyzed for the presence of chromosome alterations by two experienced scorers. The results suggest that there is the possibility of a directly proportional relationship between absorbed dose of neutron-gamma mixed field radiation and the frequency of unstable chromosome alterations analyzed in this paper. (author)

Oilseed cultivars developed from induced mutations and mutations altering fatty acid composition

International Nuclear Information System (INIS)

Bhatia, C.R.; Nichterlein, K.; Maluszynski, M.

1999-01-01

One hundred and sixty-three cultivars of annual oilseed crops, developed using induced mutations, have been officially approved and released for cultivation in 26 countries. The maximum number of cultivars have been released in soybean (58), followed by groundnut (44), sesame (16), linseed (15), rapeseed (14), Indian mustard (8), castorbean (4), white mustard (3) and sunflower (1). The majority (118 of 163) of the cultivars have been developed as direct mutants and 45 of 163 by using the induced mutants in a crossing programme. While in soybean 53 out of 58 cultivars were selected as direct mutants, in groundnut 22 from 44 were developed after hybridization. Eighty-three cultivars were developed directly by exposing seeds to gamma or X-rays. Attempts have been made to infer the successful dose range, defined as the range which led to the development, registration and release of the maximum number of mutant cultivars for gamma and X-rays. The successful dose ranges in Gy for the main oilseed crops are: soybean 100-200, groundnut 150-250, rapeseed 600-800, Indian mustard 700 and sesame 100-200. The main characteristics of the new cultivars, besides higher yield, are altered plant type, early flowering and maturity and oil content. Mutants altering fatty acid composition have been isolated in soybean, rapeseed, sunflower, linseed and minor oil crops. New cultivars having altered fatty acid composition have been released in rapeseed, sunflower and linseed. The latter, previously grown for non-edible oil, has been converted to a new edible oil crop. (author)

Transforming growth factor-β2 induces morphological alteration of human corneal endothelial cells in vitro

Directory of Open Access Journals (Sweden)

Jing Wang

2014-10-01

Full Text Available AIM:To investigate the morphological altering effect of transforming growth factor-β2 (TGF-β2 on untransfected human corneal endothelial cells (HCECs in vitro.METHODS: After untransfected HCECs were treated with TGF-β2 at different concentrations, the morphology, cytoskeleton distribution, and type IV collagen expression of the cells were examined with inverted contrast light microscopy, fluorescence microscopy, immunofluorescence or Western Blot.RESULTS:TGF-β2 at the concentration of 3-15 μg/L had obviously alterative effects on HCECs morphology in dose and time-dependent manner, and 9 μg/L was the peak concentration. TGF-β2 (9 μg/L altered HCE cell morphology after treatment for 36h, increased the mean optical density (P<0.01 and the length of F-actin, reduced the mean optical density (P<0.01 of the collagen type IV in extracellular matrix (ECM and induced the rearrangement of F-actin, microtubule in cytoplasm and collagen type IV in ECM after treatment for 72h. CONCLUTION:TGF-β2 has obviously alterative effect on the morphology of HCECs from polygonal phenotype to enlarged spindle-shaped phenotype, in dose and time-dependence manner by inducing more, elongation and alignment of F-actin, rearrangement of microtubule and larger spread area of collagen type IV.

Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish

International Nuclear Information System (INIS)

Gombeau, Kewin; Pereira, Sandrine; Ravanat, Jean-Luc; Camilleri, Virginie; Cavalie, Isabelle; Bourdineaud, Jean-Paul; Adam-Guillermin, Christelle

2016-01-01

We examined the effects of chronic exposure to different concentrations (2 and 20 μg L"−"1) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5′-CCGG-3′) and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L"−"1 DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L"−"1 DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L"−"1 DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects. - Highlights: • This study demonstrates a sex-related effect of DU exposure on DNA methylation patterns. • Impacts on DNA methylation patterns revealed a tissue-specific effect of DU exposure. • The MS–AFLP and HPLC–MS/MS sensitively and complementarily demonstrated the responses to environmental concentrations of DU.

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

Science.gov (United States)

Liu, Y; Cheng, H; Zhou, Y; Zhu, Y; Bian, R; Chen, Y; Li, C; Ma, Q; Zheng, Q; Zhang, Y; Jin, H; Wang, X; Chen, Q; Zhu, D

2013-01-01

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. PMID:23412387

Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

Directory of Open Access Journals (Sweden)

Bertrand Degos

Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing.

Science.gov (United States)

Xie, Tao; Cho, Yong Beom; Wang, Kai; Huang, Donghui; Hong, Hye Kyung; Choi, Yoon-La; Ko, Young Hyeh; Nam, Do-Hyun; Jin, Juyoun; Yang, Heekyoung; Fernandez, Julio; Deng, Shibing; Rejto, Paul A; Lee, Woo Yong; Mao, Mao

2014-10-01

Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Histone Deacetylase Inhibition Facilitates Massed Pattern-Induced Synaptic Plasticity and Memory

Science.gov (United States)

Pandey, Kiran; Sharma, Kaushik P.; Sharma, Shiv K.

2015-01-01

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well…

Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome

Directory of Open Access Journals (Sweden)

Imourana Alassane-Kpembi

2018-05-01

Full Text Available Type B trichothecene mycotoxin deoxynivalenol (DON is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae, have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE was observed after treatment by yeast only. By contrast, 3619 probes—corresponding to 2771 genes—were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes. Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome.

Science.gov (United States)

Alassane-Kpembi, Imourana; Pinton, Philippe; Hupé, Jean-François; Neves, Manon; Lippi, Yannick; Combes, Sylvie; Castex, Mathieu; Oswald, Isabelle P

2018-05-15

Type B trichothecene mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae , have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE) was observed after treatment by yeast only. By contrast, 3619 probes-corresponding to 2771 genes-were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes). Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

International Nuclear Information System (INIS)

Banerjee, Chaitali; Goswami, Ramansu; Datta, Soma; Rajagopal, R.; Mazumder, Shibnath

2011-01-01

We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca 2+ ) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca 2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca 2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca 2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

Science.gov (United States)

Khoe, Clairine V; Chung, Long H; Murray, Vincent

2018-06-01

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Effects of 4-phenyl butyric acid on high glucose-induced alterations in dorsal root ganglion neurons.

Science.gov (United States)

Sharma, Dilip; Singh, Jitendra Narain; Sharma, Shyam S

2016-12-02

Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding. 4-phenyl butyric acid (4-PBA) is a potent and selective chemical chaperone; which may inhibit ER stress. It may be hypothesized that 4-PBA could attenuate via channels in DRG in diabetic neuropathy. Effects of 4-PBA were determined by applying different parameters of oxidative stress, cell viability, apoptosis assays and channel expression in cultured DRG neurons. Hyperglycemia-induced apoptosis in the DRG neuron was inhibited by 4-PBA. Cell viability of DRG neurons was not altered by 4-PBA. Oxidative stress was significantly blocked by the 4-PBA. Sodium channel expression was not altered by the 4-PBA. Our data provide evidence that the hyperglycemia-induced alteration may be reduced by the 4-PBA without altering the sodium channel expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

Science.gov (United States)

Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

2016-04-01

DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

Influence of altered precipitation pattern on greenhouse gas emissions and soil enzyme activities in Pannonian soils

Science.gov (United States)

Forstner, Stefan Johannes; Michel, Kerstin; Berthold, Helene; Baumgarten, Andreas; Wanek, Wolfgang; Zechmeister-Boltenstern, Sophie; Kitzler, Barbara

2013-04-01

Precipitation patterns are likely to be altered due to climate change. Recent models predict a reduction of mean precipitation during summer accompanied by a change in short-term precipitation variability for central Europe. Correspondingly, the risk for summer drought is likely to increase. This may especially be valid for regions which already have the potential for rare, but strong precipitation events like eastern Austria. Given that these projections hold true, soils in this area will receive water irregularly in few, heavy rainfall events and be subjected to long-lasting dry periods in between. This pattern of drying/rewetting can alter soil greenhouse gas fluxes, creating a potential feedback mechanism for climate change. Microorganisms are the key players in most soil carbon (C) and nitrogen (N) transformation processes including greenhouse gas exchange. A conceptual model proposed by Schimel and colleagues (2007) links microbial stress-response physiology to ecosystem-scale biogeochemical processes: In order to cope with decreasing soil water potential, microbes modify resource allocation patterns from growth to survival. However, it remains unclear how microbial resource acquisition via extracellular enzymes and microbial-controlled greenhouse gas fluxes respond to water stress induced by soil drying/rewetting. We designed a laboratory experiment to test for effects of multiple drying/rewetting cycles on soil greenhouse gas fluxes (CO2, CH4, N2O, NO), microbial biomass and extracellular enzyme activity. Three soils representing the main soil types of eastern Austria were collected in June 2012 at the Lysimeter Research Station of the Austrian Agency for Health and Food Safety (AGES) in Vienna. Soils were sieved to 2mm, filled in steel cylinders and equilibrated for one week at 50% water holding capacity (WHC) for each soil. Then soils were separated into two groups: One group received water several times per week (C=control), the other group received

Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

Directory of Open Access Journals (Sweden)

Yuan Yan Sin

Full Text Available Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1, which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2 mice. The resulting mice (Arg-Cre die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.

Induced mutations for crop improvement- the generation next

International Nuclear Information System (INIS)

Bhatia, C.R.

2000-01-01

Experiments to use induced mutations for the improvement of crop plants were initiated in the country in mid nineteen fifties. After forty five years and reasonably good success stories, it is no longer an attractive subject for bright young graduate students. The areas of intellectually satisfying, contemporary, plant genetics based on induced mutations that can also bring social and commercial benefits are identified. These are: nodulation mutants in legumes, altering fatty acid composition in oil crops, modification of root characters, altering host-pathogen interactions, flowering time, day length insensitivity and some changes in modulation pattern involve mutations

Time delay induced different synchronization patterns in repulsively coupled chaotic oscillators

Science.gov (United States)

Yao, Chenggui; Yi, Ming; Shuai, Jianwei

2013-09-01

Time delayed coupling plays a crucial role in determining the system's dynamics. We here report that the time delay induces transition from the asynchronous state to the complete synchronization (CS) state in the repulsively coupled chaotic oscillators. In particular, by changing the coupling strength or time delay, various types of synchronous patterns, including CS, antiphase CS, antiphase synchronization (ANS), and phase synchronization, can be generated. In the transition regions between different synchronous patterns, bistable synchronous oscillators can be observed. Furthermore, we show that the time-delay-induced phase flip bifurcation is of key importance for the emergence of CS. All these findings may light on our understanding of neuronal synchronization and information processing in the brain.

Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

International Nuclear Information System (INIS)

Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

2004-01-01

Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

Altered regional homogeneity patterns in adults with attention-deficit hyperactivity disorder

International Nuclear Information System (INIS)

Wang, Xunheng; Jiao, Yun; Tang, Tianyu; Wang, Hui; Lu, Zuhong

2013-01-01

Purpose: Investigating the discriminative brain map for patients with attention-deficit/hyperactivity disorder (ADHD) based on feature selection and classifier; and identifying patients with ADHD based on the discriminative model. Materials and methods: A dataset of resting state fMRI contains 23 patients with ADHD and 23 healthy subjects were analyzed. Regional homogeneity (ReHo) was extracted from resting state fMRI signals and used as model inputs. Raw ReHo features were ranked and selected in a loop according to their p values. Selected features were trained and tested by support vector machines (SVM) in a cross validation procedure. Cross validation was repeated in feature selection loop to produce optimized model. Results: Optimized discriminative map indicated that the ADHD brains exhibit more increased activities than normal controls in bilateral occipital lobes and left front lobe. The altered brain regions included portions of basal ganglia, insula, precuneus, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), thalamus, and cerebellum. Correlation coefficients indicated significant positive correlation of inattentive scores with bilateral cuneus and precuneus, and significant negative correlation of hyperactive/impulsive scores with bilateral insula and claustrum. Additionally, the optimized model produced total accuracy of 80% and sensitivity of 87%. Conclusion: ADHD brain regions were more activated than normal controls during resting state. Linear support vector classifier can provide useful discriminative information of altered ReHo patterns for ADHD; and feature selection can improve the performances of classification

Altered regional homogeneity patterns in adults with attention-deficit hyperactivity disorder

Energy Technology Data Exchange (ETDEWEB)

Wang, Xunheng [School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Key Laboratory of Child Development and Learning Science (Ministry of Education), Southeast University, Nanjing 210096 (China); Jiao, Yun, E-mail: yunjiao@seu.edu.cn [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Tianyu; Wang, Hui; Lu, Zuhong [School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Key Laboratory of Child Development and Learning Science (Ministry of Education), Southeast University, Nanjing 210096 (China)

2013-09-15

Purpose: Investigating the discriminative brain map for patients with attention-deficit/hyperactivity disorder (ADHD) based on feature selection and classifier; and identifying patients with ADHD based on the discriminative model. Materials and methods: A dataset of resting state fMRI contains 23 patients with ADHD and 23 healthy subjects were analyzed. Regional homogeneity (ReHo) was extracted from resting state fMRI signals and used as model inputs. Raw ReHo features were ranked and selected in a loop according to their p values. Selected features were trained and tested by support vector machines (SVM) in a cross validation procedure. Cross validation was repeated in feature selection loop to produce optimized model. Results: Optimized discriminative map indicated that the ADHD brains exhibit more increased activities than normal controls in bilateral occipital lobes and left front lobe. The altered brain regions included portions of basal ganglia, insula, precuneus, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), thalamus, and cerebellum. Correlation coefficients indicated significant positive correlation of inattentive scores with bilateral cuneus and precuneus, and significant negative correlation of hyperactive/impulsive scores with bilateral insula and claustrum. Additionally, the optimized model produced total accuracy of 80% and sensitivity of 87%. Conclusion: ADHD brain regions were more activated than normal controls during resting state. Linear support vector classifier can provide useful discriminative information of altered ReHo patterns for ADHD; and feature selection can improve the performances of classification.

Peptide YY induces characteristic meal patterns of aged mice.

Science.gov (United States)

Mogami, Sachiko; Yamada, Chihiro; Fujitsuka, Naoki; Hattori, Tomohisa

2017-11-01

Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device. Plasma peptide YY (PYY) levels were assessed under the several feeding status or after treatment of PYY. PYY and its receptor (NPY Y2 receptor, Y2R) antagonist were intraperitoneally administered 30min before the monitoring. Although the basal 24-h meal amounts did not differ by age, the total meal time and frequency of minimum feeding activity (bout) were significantly increased and the average bout size and time per bout were significantly decreased in aged mice. PYY dynamics were abnormal and the temporal reduction in food intake by exogenous PYY was more prominent in aged mice than in young mice. PYY administration to young mice induced aged-like meal patterns, and Y2R antagonist administration to aged mice induced young-like meal patterns. Aged mice exhibited characteristic meal patterns probably due to PYY metabolism dysfunction and/or enhanced PYY-Y2R signaling, suggesting a novel method for assessing eating difficulties in aged animals and a potential target for the remedy. Copyright © 2017 Elsevier Inc. All rights reserved.

Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

Directory of Open Access Journals (Sweden)

MK Chaubey

2009-01-01

Full Text Available In the present study, Heterometrus fastigiousus venom (HFV was employed as antigen to produce species-specific scorpion antivenom (SAV in albino mice (NIH strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

Irradiation-induced patterning in dilute Cu–Fe alloys

International Nuclear Information System (INIS)

Stumphy, B.; Chee, S.W.; Vo, N.Q.; Averback, R.S.; Bellon, P.; Ghafari, M.

2014-01-01

Compositional patterning in dilute Cu 1−x Fe x (x ≈ 12%) induced by 1.8 MeV Kr + irradiation was studied as a function of temperature using atom probe tomography. Irradiation near room temperature led to homogenization of the sample, whereas irradiation at 300 °C and above led to precipitation and macroscopic coarsening. Between these two temperatures the irradiated alloys formed steady state patterns of composition where precipitates grew to a fixed size. The size in this regime increased somewhat with temperature. It was also observed that the steady state concentrations of Fe in Cu matrix and Cu in the Fe precipitates both greatly exceeded their equilibrium solubilities, with the degree of supersaturation in each phase decreasing with increasing temperature. In the macroscopic coarsening regime, the Fe-rich precipitates showed indications of a “cherry-pit” structure, with Cu precipitates forming within the Fe precipitates. In the patterning regime, interfaces between Fe-rich precipitates and the Cu-rich matrix were irregular and diffuse

Pattern-Induced Covert Category Learning in Songbirds.

Science.gov (United States)

Comins, Jordan A; Gentner, Timothy Q

2015-07-20

Language is uniquely human, but its acquisition may involve cognitive capacities shared with other species. During development, language experience alters speech sound (phoneme) categorization. Newborn infants distinguish the phonemes in all languages but by 10 months show adult-like greater sensitivity to native language phonemic contrasts than non-native contrasts. Distributional theories account for phonetic learning by positing that infants infer category boundaries from modal distributions of speech sounds along acoustic continua. For example, tokens of the sounds /b/ and /p/ cluster around different mean voice onset times. To disambiguate overlapping distributions, contextual theories propose that phonetic category learning is informed by higher-level patterns (e.g., words) in which phonemes normally occur. For example, the vowel sounds /Ι/ and /e/ can occupy similar perceptual spaces but can be distinguished in the context of "with" and "well." Both distributional and contextual cues appear to function in speech acquisition. Non-human species also benefit from distributional cues for category learning, but whether category learning benefits from contextual information in non-human animals is unknown. The use of higher-level patterns to guide lower-level category learning may reflect uniquely human capacities tied to language acquisition or more general learning abilities reflecting shared neurobiological mechanisms. Using songbirds, European starlings, we show that higher-level pattern learning covertly enhances categorization of the natural communication sounds. This observation mirrors the support for contextual theories of phonemic category learning in humans and demonstrates a general form of learning not unique to humans or language. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

Science.gov (United States)

Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Prajna, Lalitha; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Kuppamuthu, Dharmalingam

2017-01-30

Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared. A total of 1873 proteins from control and 1400 proteins from patient tear were identified by mass spectrometry. While 847 proteins were found to be glycosylated in the patient tear, only 726 were glycosylated in control tear. And, some of the tear proteins showed alterations in their glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways in antifungal defense. High levels of wound healing proteins in keratitis patient tear implied activation of tissue repair during infection. The early appearance of the host defense proteins and wound healing response indicates that tear proteins could be used as an early marker system for monitoring the progression of pathogenesis. Identification of negative regulators of the above defense pathways in keratitis tear indicates an intricate balance of pro and anti-defense mechanisms operating in fungal infection of the eye. Tear proteins from control and mycotic keratitis patients were separated into glycoproteins and non-glycosylated proteins and then identified by mass spectrometry. Tear proteins from keratitis patients showed alteration in the glycosylation pattern indicating the alteration of glycosylation machinery due to infection. Neutrophil extracellular traps specific proteins, complement pathway proteins, as well as wound healing proteins, were found only in patient tear showing the activation of antifungal defense

alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

Science.gov (United States)

Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

1996-10-01

Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

Climate induced changes in the circulation and dispersal patterns of ...

Indian Academy of Sciences (India)

Climate induced changes in the circulation and dispersal patterns of the fluvial sources during late Quaternary in the middle Bengal Fan ... in 14C dated box cores from the eastern, the central and the western regions were studied to determine ...

Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

Science.gov (United States)

Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

2016-06-01

Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Remote sensing captures varying temporal patterns of vegetation between human-altered and natural landscapes.

Science.gov (United States)

Leong, Misha; Roderick, George K

2015-01-01

Global change has led to shifts in phenology, potentially disrupting species interactions such as plant-pollinator relationships. Advances in remote sensing techniques allow one to detect vegetation phenological diversity between different land use types, but it is not clear how this translates to other communities in the ecosystem. Here, we investigated the phenological diversity of the vegetation across a human-altered landscape including urban, agricultural, and natural land use types. We found that the patterns of change in the vegetation indices (EVI and NDVI) of human-altered landscapes are out of synchronization with the phenology in neighboring natural California grassland habitat. Comparing these findings to a spatio-temporal pollinator distribution dataset, EVI and NDVI were significant predictors of total bee abundance, a relationship that improved with time lags. This evidence supports the importance of differences in temporal dynamics between land use types. These findings also highlight the potential to utilize remote sensing data to make predictions for components of biodiversity that have tight vegetation associations, such as pollinators.

Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.

Directory of Open Access Journals (Sweden)

Carlos Guerrero-Bosagna

Full Text Available Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell that influences the onset of a specific disease (male infertility. A gestating female rat (F0 generation was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell epigenome and transcriptome that correlates with adult onset disease (male infertility. The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.

Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

Science.gov (United States)

Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

2018-01-01

Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

Science.gov (United States)

Ola-Mudathir, F K; Suru, S M

2015-11-01

Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

Surface-induced patterns from evaporating droplets of aqueous carbon nanotube dispersions

KAUST Repository

Zeng, Hongbo; Kristiansen, Kai De Lange; Wang, Peng; Bergli, Joakim; Israelachvili, Jacob N.

2011-01-01

Evaporation of aqueous droplets of carbon nanotubes (CNTs) coated with a physisorbed layer of humic acid (HA) on a partially hydrophilic substrate induces the formation of a film of CNTs. Here, we investigate the role that the global geometry of the substrate surfaces has on the structure of the CNT film. On a flat mica or silica surface, the evaporation of a convex droplet of the CNT dispersion induces the well-known "coffee ring", while evaporation of a concave droplet (capillary meniscus) of the CNT dispersion in a wedge of two planar mica sheets or between two crossed-cylinder sheets induces a large area (>mm 2) of textured or patterned films characterized by different short- and long-range orientational and positional ordering of the CNTs. The resulting patterns appear to be determined by two competing or cooperative sedimentation mechanisms: (1) capillary forces between CNTs giving micrometer-sized filaments parallel to the boundary line of the evaporating droplet and (2) fingering instability at the boundary line of the evaporating droplet and subsequent pinning of CNTs on the surface giving micrometer-sized filaments of CNTs perpendicular to this boundary line. The interplay between substrate surface geometry and sedimentation mechanisms gives an extra control parameter for manipulating patterns of self-assembling nanoparticles at substrate surfaces. © 2011 American Chemical Society.

Surface-induced patterns from evaporating droplets of aqueous carbon nanotube dispersions

KAUST Repository

Zeng, Hongbo

2011-06-07

Evaporation of aqueous droplets of carbon nanotubes (CNTs) coated with a physisorbed layer of humic acid (HA) on a partially hydrophilic substrate induces the formation of a film of CNTs. Here, we investigate the role that the global geometry of the substrate surfaces has on the structure of the CNT film. On a flat mica or silica surface, the evaporation of a convex droplet of the CNT dispersion induces the well-known "coffee ring", while evaporation of a concave droplet (capillary meniscus) of the CNT dispersion in a wedge of two planar mica sheets or between two crossed-cylinder sheets induces a large area (>mm 2) of textured or patterned films characterized by different short- and long-range orientational and positional ordering of the CNTs. The resulting patterns appear to be determined by two competing or cooperative sedimentation mechanisms: (1) capillary forces between CNTs giving micrometer-sized filaments parallel to the boundary line of the evaporating droplet and (2) fingering instability at the boundary line of the evaporating droplet and subsequent pinning of CNTs on the surface giving micrometer-sized filaments of CNTs perpendicular to this boundary line. The interplay between substrate surface geometry and sedimentation mechanisms gives an extra control parameter for manipulating patterns of self-assembling nanoparticles at substrate surfaces. © 2011 American Chemical Society.

Design of Human-Machine Interface and altering of pelvic obliquity with RGR Trainer.

Science.gov (United States)

Pietrusinski, Maciej; Unluhisarcikli, Ozer; Mavroidis, Constantinos; Cajigas, Iahn; Bonato, Paolo

2011-01-01

The Robotic Gait Rehabilitation (RGR) Trainer targets secondary gait deviations in stroke survivors undergoing rehabilitation. Using an impedance control strategy and a linear electromagnetic actuator, the device generates a force field to control pelvic obliquity through a Human-Machine Interface (i.e. a lower body exoskeleton). Herein we describe the design of the RGR Trainer Human-Machine Interface (HMI) and we demonstrate the system's ability to alter the pattern of movement of the pelvis during gait in a healthy subject. Results are shown for experiments during which we induced hip-hiking - in healthy subjects. Our findings indicate that the RGR Trainer has the ability of affecting pelvic obliquity during gait. Furthermore, we provide preliminary evidence of short-term retention of the modified pelvic obliquity pattern induced by the RGR Trainer. © 2011 IEEE

Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

Science.gov (United States)

Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

2013-01-01

The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

Patterns of Seismicity Associated with USGS Identified Areas of Potentially Induced Seismicity.

Science.gov (United States)

Barnes, Caitlin; Halihan, Todd

2018-03-13

A systematic review across U.S. Geological Survey (USGS) identified potentially induced seismic locations was conducted to discover seismic distance patterns and trends over time away from injection disposal wells. Previous research indicates a 10 km (6 miles) average where the majority of induced seismicity is expected to occur within individual locations, with some areas reporting a larger radius of 35 km (22 miles) to over 70 km (43 miles). This research analyzed earthquake occurrences within nine USGS locations where specified wells were identified as contributors to induced seismicity to determine distance patterns from disposal wells or outward seismic migration over time using established principles of hydrogeology. Results indicate a radius of 31.6 km (20 miles) where 90% of felt earthquakes occur among locations, with the closest proximal felt seismic events, on average, occurring 3 km (1.9 miles) away from injection disposal wells. The results of this research found distance trends across multiple locations of potentially induced seismicity. © 2018, National Ground Water Association.

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

Science.gov (United States)

Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

2016-05-01

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Tidal-Induced Ocean Dynamics as Cause of Enceladus' Tiger Stripe Pattern

Science.gov (United States)

Vermeersen, B. L.; Maas, L. R.; van Oers, S.; Rabitti, A.; Jara-Orue, H.

2013-12-01

One of the most peculiar features on Saturn moon Enceladus is its so-called tiger stripe pattern at the geologically active South Polar Terrain (SPT), as first observed in detail by the Cassini spacecraft early 2005. It is generally assumed that the four almost parallel surface lines that constitute this pattern are faults in the icy surface overlying a confined salty water reservoir. Indeed, later Cassini observations have shown that salty water jets originate from the tiger stripes [e.g., Hansen et al., Science, 311, 1422-1425, 2006; Postberg et al., Nature, 474, 620-622, 2011]. The periodic activity of the tiger stripe faults shows a strong correlation with tidal forcing. Jets emanating from specific fault lines seem to be triggered at those places of the faults where tidal-induced stresses are largest immediately following closest orbital approach with Saturn [e.g., Hurford et al., Nature, 447, 292-294, 2007]. Thus jet activity seems to be directly induced by tidal forcing. However, this does not explain the characteristic regular pattern of the stripes themselves. Here we explore the possibility that this pattern is formed and maintained by induced, tidally and rotationally driven, fluid motions in the ocean underneath the icy surface of the tiger-stripe region. The remarkable spatial regularity of Enceladus' SPT fault lines is reminiscent of that observed at the surface of confined density-stratified fluids by the action of induced internal gravity waves. Theoretical analysis, numerical simulations and laboratory water tank experiments all indicate that wave attractors - particular limit orbits to which waves are focused in a fluid basin - naturally emerge in gravitationally (radial salt concentration or temperature differences) or rotationally stratified confined fluids as a function of forcing periodicity and fluid basin geometry [Maas et al., Nature, 338, 557-561, 1997]. We have found that ocean dynamical wave attractors induced by tidal-effective forcing

Does altered protein metabolism interfere with postmortem degradation analysis for PMI estimation?

Science.gov (United States)

Zissler, A; Ehrenfellner, B; Foditsch, E E; Monticelli, F C; Pittner, S

2018-03-02

An accurate estimation of the postmortem interval (PMI) is a central aspect in forensic routine. Recently, a novel approach based on the analysis of postmortem muscle protein degradation has been proposed. However, a number of questions remain to be answered until sensible application of this method to a broad variety of forensic cases is possible. To evaluate whether altered in vivo protein metabolism interferes with postmortem degradation patterns, we conducted a comparative study. We developed a standardized animal degradation model in rats, and collected additional muscle samples from animals recovering from muscle injury and from rats with developed disuse muscle atrophy after induced spinal cord injury. All samples were analyzed by SDS-PAGE and Western blot, labeling well-characterized muscle proteins. Tropomyosin was found to be stable throughout the investigated PMI and no alterations were detected in regenerating and atrophic muscles. In contrast, significant predictable postmortem changes occurred in desmin and vinculin protein band patterns. While no significant deviations from native patterns were detected in at-death samples of disuse muscle atrophy, interestingly, samples of rats recovering from muscle injury revealed additional desmin and vinculin degradation bands that did not occur in this form in any of the examined postmortem samples regardless of PMI. It remains to be investigated whether in vivo-altered metabolism influences postmortem degradation kinetics or if such muscle samples undergo postmortem degradation in a regular fashion.

Relativity-Induced Bonding Pattern Change in Coinage Metal Dimers M2 (M = Cu, Ag, Au, Rg).

Science.gov (United States)

Li, Wan-Lu; Lu, Jun-Bo; Wang, Zhen-Ling; Hu, Han-Shi; Li, Jun

2018-05-07

The periodic table provides a fundamental protocol for qualitatively classifying and predicting chemical properties based on periodicity. While the periodic law of chemical elements had already been rationalized within the framework of the nonrelativistic description of chemistry with quantum mechanics, this law was later known to be affected significantly by relativity. We here report a systematic theoretical study on the chemical bonding pattern change in the coinage metal dimers (Cu 2 , Ag 2 , Au 2 , Rg 2 ) due to the relativistic effect on the superheavy elements. Unlike the lighter congeners basically demonstrating ns- ns bonding character and a 0 g + ground state, Rg 2 shows unique 6d-6d bonding induced by strong relativity. Because of relativistic spin-orbit (SO) coupling effect in Rg 2 , two nearly degenerate SO states, 0 g + and 2 u , exist as candidate of the ground state. This relativity-induced change of bonding mechanism gives rise to various unique alteration of chemical properties compared with the lighter dimers, including higher intrinsic bond energy, force constant, and nuclear shielding. Our work thus provides a rather simple but clear-cut example, where the chemical bonding picture is significantly changed by relativistic effect, demonstrating the modified periodic law in heavy-element chemistry.

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

Alteration of sheep coat color pattern by disruption of ASIP gene via CRISPR Cas9.

Science.gov (United States)

Zhang, Xuemei; Li, Wenrong; Liu, Chenxi; Peng, Xinrong; Lin, Jiapeng; He, Sangang; Li, Xuejiao; Han, Bing; Zhang, Ning; Wu, Yangsheng; Chen, Lei; Wang, Liqin; MaYila; Huang, Juncheng; Liu, Mingjun

2017-08-15

Coat color is an important characteristic and economic trait in domestic sheep. Aiming at alteration of Chinese merino sheep coat color by genome manipulation, we disrupted sheep agouti signaling protein gene by CRISPR/Cas9. A total of seven indels were identified in 5 of 6 born lambs. Each targeted lamb happened at least two kinds of modifications, and targeted lambs with multiple modifications displayed variety of coat color patterns. Three lambs with 4 bp deletion showed badgerface with black body coat color in two lambs, and brown coat color with light ventral pigmentation in another one. The black-white spotted color was observed in two lambs with 2 bp deletion. Further analysis unraveled that modifications happened in one or more than two copies of ASIP gene, and moreover, the additional spontaneous mutations of D 9 and/or D 5 preceding the targeting modification could also involve the formation of coat color patterns. Taken together, the entanglement of ASIP modifications by CRISPR/Cas9, spontaneous D 9 /D 5 mutations, and ASIP gene duplications contributed to the variety of coat color patterns in targeted lambs.

Alteration of human serum albumin binding properties induced by modifications: A review

Science.gov (United States)

Maciążek-Jurczyk, Małgorzata; Szkudlarek, Agnieszka; Chudzik, Mariola; Pożycka, Jadwiga; Sułkowska, Anna

2018-01-01

Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

Alteration of cerebrovascular haemodynamic patterns due to atrial fibrillation: an in silico investigation.

Science.gov (United States)

Scarsoglio, S; Saglietto, A; Anselmino, M; Gaita, F; Ridolfi, L

2017-04-01

There has recently been growing evidence that atrial fibrillation (AF), the most common cardiac arrhythmia, is independently associated with the risk of dementia. This represents a very recent frontier with high social impact for the number of individuals involved and for the expected increase in AF incidence in the next 40 years. Although a number of potential haemodynamic processes, such as microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise as connecting links between the two pathologies, the causal mechanisms are far from clear. An in silico approach is proposed that combines in sequence two lumped-parameter schemes, for the cardiovascular system and the cerebral circulation. The systemic arterial pressure is obtained from the cardiovascular system and used as the input for the cerebral circulation, with the aim of studying the role of AF on the cerebral haemodynamics with respect to normal sinus rhythm (NSR), over a 5000 beat recording. In particular, the alteration of the haemodynamic (pressure and flow rate) patterns in the microcirculation during AF is analysed by means of different statistical tools, from correlation coefficients to autocorrelation functions, crossing times, extreme values analysis and multivariate linear regression models. A remarkable signal alteration, such as a reduction in signal correlation (NSR, about 3 s; AF, less than 1 s) and increased probability (up to three to four times higher in AF than in NSR) of extreme value events, emerges for the peripheral brain circulation. The described scenario offers a number of plausible cause-effect mechanisms that might explain the occurrence of critical events and the haemodynamic links relating to AF and dementia. © 2017 The Author(s).

Plant Species Rather Than Climate Greatly Alters the Temporal Pattern of Litter Chemical Composition During Long-Term Decomposition

Science.gov (United States)

Li, Yongfu; Chen, Na; Harmon, Mark E.; Li, Yuan; Cao, Xiaoyan; Chappell, Mark A.; Mao, Jingdong

2015-10-01

A feedback between decomposition and litter chemical composition occurs with decomposition altering composition that in turn influences the decomposition rate. Elucidating the temporal pattern of chemical composition is vital to understand this feedback, but the effects of plant species and climate on chemical changes remain poorly understood, especially over multiple years. In a 10-year decomposition experiment with litter of four species (Acer saccharum, Drypetes glauca, Pinus resinosa, and Thuja plicata) from four sites that range from the arctic to tropics, we determined the abundance of 11 litter chemical constituents that were grouped into waxes, carbohydrates, lignin/tannins, and proteins/peptides using advanced 13C solid-state NMR techniques. Decomposition generally led to an enrichment of waxes and a depletion of carbohydrates, whereas the changes of other chemical constituents were inconsistent. Inconsistent convergence in chemical compositions during decomposition was observed among different litter species across a range of site conditions, whereas one litter species converged under different climate conditions. Our data clearly demonstrate that plant species rather than climate greatly alters the temporal pattern of litter chemical composition, suggesting the decomposition-chemistry feedback varies among different plant species.

Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito.

Directory of Open Access Journals (Sweden)

Lixin Wang

Full Text Available Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT, a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery. RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON, paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W, lateral periaqueduct gray (PAG, lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS. RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration and satiety (meal interval and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

Science.gov (United States)

Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationships between hippocampal activity and breathing patterns

DEFF Research Database (Denmark)

Harper, R M; Poe, G R; Rector, D M

1998-01-01

Single cell discharge, EEG activity, and optical changes accompanying alterations in breathing patterns, as well as the knowledge that respiratory musculature is heavily involved in movement and other behavioral acts, implicate hippocampal regions in some aspects of breathing control. The control...... is unlikely to reside in oscillatory breathing movements, because such patterns emerge in preparations retaining only the medulla (and perhaps only the spinal cord). However, momentary changes in breathing patterns induced by affect, startle, whole-body movement changes, or compensatory ventilatory changes...... of hippocampal contributions to breathing control should be viewed in the context that significant interactions exist between blood pressure changes and ventilation, and that modest breathing challenges, such as exposure to hypercapnia or to increased resistive loads, bring into action a vast array of brain...

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning.

Science.gov (United States)

Galloway, Jenna L; Delgado, Irene; Ros, Maria A; Tabin, Clifford J

2009-07-16

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.

Design of Human – Machine Interface and Altering of Pelvic Obliquity with RGR Trainer

Science.gov (United States)

Pietrusinski, Maciej; Unluhisarcikli, Ozer; Mavroidis, Constantinos; Cajigas, Iahn; Bonato, Paolo

2012-01-01

The Robotic Gait Rehabilitation (RGR) Trainer targets secondary gait deviations in stroke survivors undergoing rehabilitation. Using an impedance control strategy and a linear electromagnetic actuator, the device generates a force field to control pelvic obliquity through a Human-Machine Interface (i.e. a lower body exoskeleton). Herein we describe the design of the RGR Trainer Human-Machine Interface (HMI) and we demonstrate the system’s ability to alter the pattern of movement of the pelvis during gait in a healthy subject. Results are shown for experiments during which we induced hip-hiking – in healthy subjects. Our findings indicate that the RGR Trainer has the ability of affecting pelvic obliquity during gait. Furthermore, we provide preliminary evidence of short-term retention of the modified pelvic obliquity pattern induced by the RGR Trainer. PMID:22275693

Brief rewarming blunts hypothermia-induced alterations in sensation, motor drive and cognition

Directory of Open Access Journals (Sweden)

Marius Brazaitis

2016-12-01

hypothermia-induced alterations in neural drive transmission (4.3±0.5 versus 3.4±0.8 mV H-reflex and 4.9±0.2 versus 4.4±0.4 mV V-wave, P<0.05, which increased central fatigue during a 2-min maximum load (P<0.05. Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P<0.05.Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for thermoregulation, sensation, motor drive and cognition, despite the fact that rectal and deep muscle temperature remained lowered.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

Science.gov (United States)

Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

2013-09-01

To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

Patterns of gravity induced aggregate migration during casting of fluid concretes

DEFF Research Database (Denmark)

Spangenberg, Jon; Roussel, N.; Hattel, Jesper Henri

2012-01-01

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in...

Effect of Admixed Micelles on the Microstructure Alterations of Reinforced Mortar Subjected to Chloride Induced Corrosion

NARCIS (Netherlands)

Hu, J.; Koleva, D.A.; Van Breugel, K.

2011-01-01

This paper reports the main results from the influence of the initially admixed nano-aggregates (0.5 g/l PEO113-b-PS70 micelles previously dissolved in demi-water) on microstructural alterations of the reinforced mortar subjected to chloride induced corrosion. The morphology of hydration/corrosion

Altered trunk muscle recruitment patterns during lifting in individuals in remission from recurrent low back pain.

Science.gov (United States)

Suehiro, Tadanobu; Ishida, Hiroshi; Kobara, Kenichi; Osaka, Hiroshi; Watanabe, Susumu

2018-04-01

Changes in the recruitment pattern of trunk muscles may contribute to the development of recurrent or chronic symptoms in people with low back pain (LBP). However, the recruitment pattern of trunk muscles during lifting tasks associated with a high risk of LBP has not been clearly determined in recurrent LBP. The present study aimed to investigate potential differences in trunk muscles recruitment patterns between individuals with recurrent LBP and asymptomatic individuals during lifting. The subjects were 25 individuals with recurrent LBP and 20 asymptomatic individuals. Electromyography (EMG) was used to measure onset time, EMG amplitude, overall activity of abdominal muscles, and overall activity of back muscles during a lifting task. The onsets of the transversus abdominis/internal abdominal oblique and multifidus were delayed in the recurrent LBP group despite remission from symptoms. Additionally, the EMG amplitudes of the erector spinae, as well as the overall activity of abdominal muscles or back muscles, were greater in the recurrent LBP group. No differences in EMG amplitude of the external oblique, transversus abdominis/internal abdominal oblique, and multifidus were found between the groups. Our findings indicate the presence of an altered trunk muscle recruitment pattern in individuals with recurrent LBP during lifting. Copyright © 2018 Elsevier Ltd. All rights reserved.

Salicylic acid-induced germination, biochemical and developmental alterations in rye (Secale cereale L.)

OpenAIRE

Yanik, Fatma; Aytürk, Özlem; Çetinbaş-Genç, Aslihan; Vardar, Filiz

2018-01-01

Salicylic acid (SA) is one of the endogenous plant growth regulators that modulate various metabolic and physiological events. To evaluate the exogenous SA-induced germination, biochemical and developmental alterations, different concentrations (10, 100, 500 and 1000 μM) of SA were applied to rye (Secale cereale L.) seeds in hydroponic culture conditions for 15 days. The observations revealed that seed germination and root elongation were stimulated in 10 μM SA treatment, however they were in...

Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain.

Directory of Open Access Journals (Sweden)

Katrina Weston-Green

Full Text Available BACKGROUND/AIM: Second generation antipsychotics (SGAs are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. METHODOLOGY/RESULTS: Levels of pro-opiomelanocortin (POMC, neuropeptide Y (NPY and glutamic acid decarboxylase (GAD(65, enzyme for GABA synthesis mRNA expression, and cannabinoid CB1 receptor (CB1R binding density (using [(3H]SR-141716A were examined in the arcuate nucleus (Arc and dorsal vagal complex (DVC of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days. Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. CONCLUSIONS: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.

Selective wetting-induced micro-electrode patterning for flexible micro-supercapacitors.

Science.gov (United States)

Kim, Sung-Kon; Koo, Hyung-Jun; Lee, Aeri; Braun, Paul V

2014-08-13

Selective wetting-induced micro-electrode patterning is used to fabricate flexible micro-supercapacitors (mSCs). The resulting mSCs exhibit high performance, mechanical stability, stable cycle life, and hold great promise for facile integration into flexible devices requiring on-chip energy storage. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Secondhand tobacco smoke, arterial stiffness, and altered circadian blood pressure patterns are associated with lung inflammation and oxidative stress in rats.

Science.gov (United States)

Gentner, Nicole J; Weber, Lynn P

2012-02-01

Chronic smoking and secondhand tobacco smoke exposure are major risk factors for cardiovascular disease that are known to adversely alter the structural and mechanical properties of arteries. The objective of this study was to determine the effects of subchronic secondhand tobacco smoke exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in conscious, unsedated radiotelemetry-implanted rats. Pulse wave change in pressure over time (dP/dt) was used an indicator of arterial stiffness and was compared with both structural (wall thickness) and functional (nitric oxide production and bioactivity and endothelin-1 levels) features of the arterial wall. In addition, histology of lung, heart, and liver was examined as well as pulmonary and hepatic detoxifying enzyme activity (cytochrome P450, specifically CYP1A1). Subchronic secondhand tobacco smoke exposure altered the circadian pattern of heart rate and blood pressure, with a loss in the normal dipping pattern of blood pressure during sleep. Secondhand tobacco smoke exposure also increased pulse wave dP/dt in the absence of any structural modifications in the arterial wall. Furthermore, although nitric oxide production and endothelin-1 levels were not altered by secondhand tobacco smoke, there was increased inactivation of nitric oxide as indicated by peroxynitrite production. Increased lung neutrophils or pulmonary CYP1A1 may be responsible for the increase in oxidative stress in rats exposed to secondhand tobacco smoke. In turn, this may be related to the observed failure of blood pressure to dip during periods of sleep and a possible increase in arterial stiffness.

Interleukin 1α-Deficient Mice Have an Altered Gut Microbiota Leading to Protection from Dextran Sodium Sulfate-Induced Colitis.

Science.gov (United States)

Nunberg, Moran; Werbner, Nir; Neuman, Hadar; Bersudsky, Marina; Braiman, Alex; Ben-Shoshan, Moshe; Ben Izhak, Meirav; Louzoun, Yoram; Apte, Ron N; Voronov, Elena; Koren, Omry

2018-01-01

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1�

Comparison of hydrothermal alteration patterns associated with porphyry Cu deposits hosted by granitoids and intermediate-mafic volcanic rocks, Kerman Magmatic Arc, Iran: Application of geological, mineralogical and remote sensing data

Science.gov (United States)

Yousefi, Seyyed Jabber; Ranjbar, Hojjatollah; Alirezaei, Saeed; Dargahi, Sara; Lentz, David R.

2018-06-01

The southern section of the Cenozoic Urumieh-Dokhtar Magmatic Arc (UDMA) of Iran, known as Kerman Magmatic Arc (KMA) or Kerman copper belt, is a major host to porphyry Cu ± Mo ± Au deposits, collectively known as PCDs. In this study, the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and spectral angle mapper (SAM) method, combined with field data, mineralogical studies, and spectral analysis are used to determine hydrothermal alteration patterns related to PCDs in the KMA. Gossans developed over some of these porphyry type deposits were mapped using Landsat 8 data. In the NKMA gossans are more developed than in the SKMA due to comparatively lower rate of erosion. The hydrothermal alteration pattern mapped by ASTER data were evaluated using mineralogical and spectral data. ASTER data proved to be useful for mapping the hydrothermal alteration in this semi-arid type of climate. Also Landsat 8 was useful for mapping the iron oxide minerals in the gossans that are associated with the porphyry copper deposits. Our multidisciplinary approach indicates that unlike the PCDs in the northern KMA that are associated with distinct and widespread propylitic alteration, those in the granitoid country rocks lack propylitic alteration or the alteration is only weakly and irregularly developed. The porphyry systems in southern KMA are further distinguished by development of quartz-rich phyllic alteration zones in the outer parts of the PCDs that could be mapped using remote sensing data. Consideration of variations in alteration patterns and specific alteration assemblages are critical in regional exploration for PCDs.

Interfacial patterns in magnetorheological fluids: Azimuthal field-induced structures.

Science.gov (United States)

Dias, Eduardo O; Lira, Sérgio A; Miranda, José A

2015-08-01

Despite their practical and academic relevance, studies of interfacial pattern formation in confined magnetorheological (MR) fluids have been largely overlooked in the literature. In this work, we present a contribution to this soft matter research topic and investigate the emergence of interfacial instabilities when an inviscid, initially circular bubble of a Newtonian fluid is surrounded by a MR fluid in a Hele-Shaw cell apparatus. An externally applied, in-plane azimuthal magnetic field produced by a current-carrying wire induces interfacial disturbances at the two-fluid interface, and pattern-forming structures arise. Linear stability analysis, weakly nonlinear theory, and a vortex sheet approach are used to access early linear and intermediate nonlinear time regimes, as well as to determine stationary interfacial shapes at fully nonlinear stages.

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

Science.gov (United States)

Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2008-04-18

Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Sex-related differences in cadmium-induced alteration of drug action in the rat

Energy Technology Data Exchange (ETDEWEB)

Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

1976-01-01

Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

Science.gov (United States)

Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

1997-01-01

The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

Science.gov (United States)

Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

1988-04-01

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Fungal innate immunity induced by bacterial microbe-associated molecular patterns (MAMPs)

DEFF Research Database (Denmark)

Ip Cho, Simon; Sundelin, Thomas; Erbs, Gitte

2016-01-01

Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposin...

The ultrastructural alterations in rat corneas with experimentally-induced diabetes mellitus

International Nuclear Information System (INIS)

Take, G.; Karabay, G.; Erdogan, D.; Duyar, I.

2006-01-01

To examine the ultrastructural changes of rat corneas in streptozotocin (STZ) induced diabetes mellitus and the and the follow-up insulin treatment. Sprague-Dawley type rats were used for experimental procedures during the period from January to April 2003 at Baskent University, Ankara, Turkey. Rats were studied in four groups: group 1: controls, group 2 sham controls (single dose IV sodium citrate); group 3 STZ-induced diabetes mellitus (Single dose 45mg/kg STZ intravenously), group 4: diabetes mellitus + insulin treatment (8U/day). We observed degenerative changes in the epithelial layer, stromal keratocytes and endothelial cells in diabetic group. In contrast, the corneal layers have revealed positive alterations in the insulin-treated group. The statistical analysis, showed significant narrowing in the epithelial layer in the diabetic group (p0.02), whereas thickening was observed in the epithelial basement membrane and Descemet's membrane (p=0.002). It was determined that that diabetes mellitus causes degenerative changes in cornea, which are positively influenced by short-term insulin treatment. (author)

High-protein diet improves sensitivity to cholecystokinin and shifts the cecal microbiome without altering brain inflammation in diet-induced obesity in rats.

Science.gov (United States)

Wang, Lixin; Jacobs, Jonathan P; Lagishetty, Venu; Yuan, Pu-Qing; Wu, Shuping V; Million, Mulugeta; Reeve, Joseph R; Pisegna, Joseph R; Taché, Yvette

2017-10-01

High-protein diet (HPD) curtails obesity and/or fat mass, but it is unknown whether it reverses neuroinflammation or alters glucose levels, CCK sensitivity, and gut microbiome in rats fed a Western diet (WD)-induced obesity (DIO). Male rats fed a WD (high fat and sugar) for 12 wk were switched to a HPD for 6 wk. Body composition, food intake, meal pattern, sensitivity to intraperitoneal CCK-8S, blood glucose, brain signaling, and cecal microbiota were assessed. When compared with a normal diet, WD increased body weight (9.3%) and fat mass (73.4%). CCK-8S (1.8 or 5.2 nmol/kg) did not alter food intake and meal pattern in DIO rats. Switching to a HPD for 6 wk reduced fat mass (15.7%) with a nonsignificantly reduced body weight gain, normalized blood glucose, and decreased feeding after CCK-8S. DIO rats on the WD or switched to a HPD showed comparable microbial diversity. However, in HPD versus WD rats, there was enrichment of 114 operational taxonomic units (OTUs) and depletion of 188 OTUs. Of those, Akkermansia muciniphila (enriched on a HPD), an unclassified Clostridiales, a member of the RF39 order, and a Phascolarctobacterium were significantly associated with fat mass. The WD increased cytokine expression in the hypothalamus and dorsal medulla that was unchanged by switching to HPD. These data indicate that HPD reduces body fat and restores glucose homeostasis and CCK sensitivity, while not modifying brain inflammation. In addition, expansion of cecal Akkermansia muciniphila correlated to fat mass loss may represent a potential peripheral mechanism of HPD beneficial effects.

Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats

International Nuclear Information System (INIS)

Femia, Angelo Pietro; Luceri, Cristina; Toti, Simona; Giannini, Augusto; Dolara, Piero; Caderni, Giovanna

2010-01-01

Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to

Magnetic field is the dominant factor to induce the response of Streptomyces avermitilis in altered gravity simulated by diamagnetic levitation.

Directory of Open Access Journals (Sweden)

Mei Liu

Full Text Available BACKGROUND: Diamagnetic levitation is a technique that uses a strong, spatially varying magnetic field to simulate an altered gravity environment, as in space. In this study, using Streptomyces avermitilis as the test organism, we investigate whether changes in magnetic field and altered gravity induce changes in morphology and secondary metabolism. We find that a strong magnetic field (12T inhibit the morphological development of S. avermitilis in solid culture, and increase the production of secondary metabolites. METHODOLOGY/PRINCIPAL FINDINGS: S. avermitilis on solid medium was levitated at 0 g*, 1 g* and 2 g* in an altered gravity environment simulated by diamagnetic levitation and under a strong magnetic field, denoted by the asterix. The morphology was obtained by electromicroscopy. The production of the secondary metabolite, avermectin, was determined by OD(245 nm. The results showed that diamagnetic levitation could induce a physiological response in S. avermitilis. The difference between 1 g* and the control group grown without the strong magnetic field (1 g, showed that the magnetic field was a more dominant factor influencing changes in morphology and secondary metabolite production, than altered gravity. CONCLUSION/SIGNIFICANCE: We have discovered that magnetic field, rather than altered gravity, is the dominant factor in altered gravity simulated by diamagnetic levitation, therefore care should to be taken in the interpretation of results when using diamagnetic levitation as a technique to simulate altered gravity. Hence, these results are significant, and timely to researchers considering the use of diamagnetic levitation to explore effects of weightlessness on living organisms and on physical phenomena.

Proteomic Alterations in Response to Hypoxia Inducible Factor 2α in Normoxic Neuroblastoma Cells.

Science.gov (United States)

Cimmino, Flora; Pezone, Lucia; Avitabile, Marianna; Persano, Luca; Vitale, Monica; Sassi, Mauro; Bresolin, Silvia; Serafin, Valentina; Zambrano, Nicola; Scaloni, Andrea; Basso, Giuseppe; Iolascon, Achille; Capasso, Mario

2016-10-07

Hypoxia inducible factor (HIF)-2α protein expression in solid tumors promotes stem-like phenotype in cancer stem cells and increases tumorigenic potential in nonstem cancer cells. Recently, we have shown that HIF-1/2α gene expression is correlated to neuroblastoma (NB) poor survival and to undifferentiated tumor state; HIF-2α protein was demonstrated to enhance aggressive features of the disease. In this study, we used proteomic experiments on NB cells to investigate HIF-2α downstream-regulated proteins or pathways with the aim of providing novel therapeutic targets or bad prognosis markers. We verified that pathways mostly altered by HIF-2α perturbation are involved in tumor progression. In particular, HIF-2α induces alteration of central metabolism and splicing control pathways. Simultaneously, WNT, RAS/MAPK, and PI3K/AKT activity or expression are affected and may impact the sensitivity and the intensity of HIF-2α-regulated pathways. Furthermore, genes coding the identified HIF-2α-related markers built a signature able to stratify NB patients with unfavorable outcome. Taken together, our findings underline the relevance of dissecting the downstream effects of a poor survival marker in developing targeted therapy and improving patient stratification. Future prospective studies are needed to translate the use of these data into the clinical practice.

Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study

Directory of Open Access Journals (Sweden)

Rafati A.

2015-09-01

Full Text Available Introduction: The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog’s isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz. Materials and Methods: Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF radiation emitted from a common Jammer at a distance of 1m from the jammer’s antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T, the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz as stimuli. Results: The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. Conclusion: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study.

Science.gov (United States)

Rafati, A; Rahimi, S; Talebi, A; Soleimani, A; Haghani, M; Mortazavi, S M J

2015-09-01

The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer's antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

Effect of Acute Alterations in Foot Strike Patterns during Running on Sagittal Plane Lower Limb Kinematics and Kinetics.

Science.gov (United States)

Valenzuela, Kevin A; Lynn, Scott K; Mikelson, Lisa R; Noffal, Guillermo J; Judelson, Daniel A

2015-03-01

The purpose of this study was to determine the effect of foot strike patterns and converted foot strike patterns on lower limb kinematics and kinetics at the hip, knee, and ankle during a shod condition. Subjects were videotaped with a high speed camera while running a 5km at self-selected pace on a treadmill to determine natural foot strike pattern on day one. Preferred forefoot group (PFFG, n = 10) and preferred rear foot group (PRFG, n = 11) subjects were identified through slow motion video playback (n = 21, age = 22.8±2.2 years, mass = 73.1±14.5 kg, height 1.75 ± 0.10 m). On day two, subjects performed five overground run trials in both their natural and unnatural strike patterns while motion and force data were collected. Data were collected over two days so that foot strike videos could be analyzed for group placement purposes. Several 2 (Foot Strike Pattern -forefoot strike [FFS], rearfoot strike [RFS]) x 2 (Group - PFFG, PRFG) mixed model ANOVAs (p strike patterns during shod running can create alterations in certain lower limb kinematic and kinetic measures that are not dependent on the preferred foot strike pattern of the individual. This research also challenges the contention that the impact transient spike in the vertical ground reaction force curve is only present during a rear foot strike type of running gait. Key pointsFootstrike pattern changes should be individually considered and implemented based on individual histories/abilitiesForefoot strike patterns increase external dorsiflexion momentsRearfoot strike patterns increase external knee flexion momentsRecreational shod runners are able to mimic habitual mechanics of different foot strike patterns.

Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

Science.gov (United States)

Otaki, Joji M

2008-07-01

A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes.

Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

Science.gov (United States)

Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

2015-07-01

Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Rosemary leaves extract against radiation-induced hematological and biochemical alterations in mice

Directory of Open Access Journals (Sweden)

Acharya Garima S.

2008-01-01

Full Text Available The present paper is a study of the modulatory effect of Rosmarinus officinalis leaves extract on radiation-induced hematological and biochemical changes in Swiss albino mice. The dose reduction factor for the Rosemary extract against gamma rays was calculated 1.53 from LD50/30 values. The Rosemary extract was administered orally for 5 consecutive days prior to radiation exposure. The hematological and biochemical parameters were assessed from day 1 to 30 post-irradiation intervals. The total erythrocyte count, total leucocytes count, hemoglobin, and hematocrit values in the experimental group were found to be elevated as compared to the control group of mice. Furthermore, the Rosemary extract treatment enhanced reduced glutathione content in the liver and blood against radiation-induced depletion. Treatment with the plant extract brought a significant fall in the lipid peroxidation level, suggesting rosemary's role in protection against radiation-induced membrane and cellular damage. The results from the present study suggest a radio-protective effect of the Rosemary extract against radiation-induced hematological and biochemical alterations in mice.

Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1.

Science.gov (United States)

Rodrigues, Elizabeth M; Scudder, Samantha L; Goo, Marisa S; Patrick, Gentry N

2016-02-03

Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. Copyright © 2016 the authors 0270-6474/16/361590-06$15.00/0.

On the origin of deformation-induced rotation patterns below nanoindents

International Nuclear Information System (INIS)

Zaafarani, N.; Raabe, D.; Roters, F.; Zaefferer, S.

2008-01-01

This study is about the origin of systematic deformation-induced crystallographic orientation patterns around nanoindents (here of single crystalline copper; conical indenter) using the following approach: first, the rotation pattern is investigated in three-dimensions (3D) using a high-resolution 3D electron backscattered diffraction (EBSD) technique (EBSD tomography) which works by a serial sectioning and EBSD mapping procedure in a scanning electron microscopy-focused ion beam cross-beam set-up. Second, the problem is modeled using a crystal plasticity finite element method which is based on a dislocation density-based constitutive model. Third, the results were discussed in terms of a geometrical model which simplifies the boundary conditions during indentation in terms of a compressive state normal to the local tangent of the indent shape. This simplification helps to identify the dominant slip systems and the resulting lattice rotations, thereby allowing us to reveal the basic mechanism of the formation of the rotation patterns. The finite element simulations also predict the pile-up patterning around the indents, which can be related to the dislocation density evolution

Dietary obesity caused by a specific circadian eating pattern.

Science.gov (United States)

Hariri, Niloofar; Thibault, Louise

2011-04-01

The eating pattern is altered by high-fat diet-induced obesity. To clarify whether this is dependent on the fatty acid profile of the diet, the authors conducted two studies on adult female Sprague-Dawley rats fed normal-fat chow or high-fat diets with varying fatty acid composition. Eating pattern and body weight were assessed in rats fed canola-based (low in saturated fatty acids) or lard-based (moderate in saturated fatty acids) diets for 7 days, and in animals fed chow or canola- or butter-based diets (rich in saturated fatty acids) for 43 days. These parameters were also determined when restricted amounts of low-fat canola- or butter-based diets were consumed for 25 days. Early exposure to canola or lard high-fat feeding or prolonged access to canola- or butter-based fat-rich diets (relative to chow feeding) did not alter the normal light-dark distribution of food and energy intake. All animals ingested most of their food during the dark phase. However, feeding the high-fat canola- and butter-based diets produced an altered eating pattern during the light phase characterized by a smaller number of meals, longer intermeal interval, and enhanced satiety ratio, and consumption of shorter-lasting meals than chow-fed animals. Relative to canola or chow feeding, butter-fed animals consumed a lower number of meals during the dark phase and had a higher eating rate in the light phase, but ate larger meals overall. Only butter feeding led to overeating and obesity. When given a restricted amount of low-fat canola- or butter-based diet at the start of the light phase, rats ate most of their food in that phase and diurnal rather than nocturnal feeding occurred with restriction. These findings underscore the role of saturated fatty acids and the resulting eating pattern alteration in the development of obesity.

Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase

Science.gov (United States)

Engelmann, Alexander J.; Aparicio, Mark B.; Kim, Airee; Sobieraj, Jeffery C.; Yuan, Clara J.; Grant, Yanabel

2013-01-01

We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6 weeks. A set of WR rats were injected with 5-bromo-2′-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6 h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake

A Reevaluation of X-Irradiation Induced Phocomelia and Proximodistal Limb Patterning

Science.gov (United States)

Galloway, Jenna L.; Delgado, Irene; Ros, Maria A.; Tabin, Clifford J.

2009-01-01

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3-5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the Progress Zone Model, which states that a cell’s proximodistal (PD) identity is determined by the length of time spent in a distal limb region termed the “Progress Zone” 7. Indeed, studies of X-irradiation induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the Progress Zone Model. Here, using a combination of molecular analysis and lineage tracing, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. As skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the etiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that PD patterning is unaffected following X-irradiation does not support the predictions of the Progress Zone

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

Energy Technology Data Exchange (ETDEWEB)

Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

International Nuclear Information System (INIS)

Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

2012-01-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

Directory of Open Access Journals (Sweden)

Tuisku Katinka

2008-04-01

Full Text Available Abstract Background Neuroleptic-induced movement disorders (NIMDs have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV. Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA and pseudoakathisia (PsA were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats

International Nuclear Information System (INIS)

Picard, C.

2000-12-01

Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT 3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

Science.gov (United States)

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

Saccharomyces cerevisiae mutants with enhanced induced mutation and altered mitotic gene conversion.

Science.gov (United States)

Ivanov, E L; Kovaltzova, S V; Korolev, V G

1989-08-01

We have developed a method to isolate yeast (Saccharomyces cerevisiae) mutants with enhanced induced mutagenesis based on nitrous acid-induced reversion of the ade2-42 allele. Six mutants have been isolated and designated him (high induced mutagenesis), and 4 of them were studied in more detail. The him mutants displayed enhanced reversion of the ade2-42 allele, either spontaneous or induced by nitrous acid, UV light, and the base analog 6-N-hydroxylaminopurine, but not by gamma-irradiation. It is worth noting that the him mutants turned out not to be sensitive to the lethal effects of the mutagens used. The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes). The latter agent revealed the most apparent differences between the him mutants and the wild-type strain and was, therefore, chosen for the genetic analysis of mutants, him mutations analyzed behaved as a single Mendelian trait; complementation tests indicated 3 complementation groups (HIM1, HIM2, and HIM3), each containing 1 mutant allele. Uracil-DNA glycosylase activity was determined in crude cell extracts, and no significant differences between the wild-type and him strains were detected. Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination. Genetic evidence strongly suggests him mutations to be involved in a process of mismatch correction of molecular heteroduplexes.

Maternal hyperthyroidism alters the pattern of expression of cardiac renin-angiotensin system components in rat offspring.

Science.gov (United States)

Lino, Caroline A; Shibata, Caroline E R; Barreto-Chaves, Maria Luiza M

2014-03-01

Changes in perinatal environment can lead to physiological, morphological, or metabolic alterations in adult life. It is well known that thyroid hormones (TH) are critical for the development, growth, and maturation of organs and systems. In addition, TH interact with the renin-angiotensin system (RAS), and both play a critical role in adult cardiovascular function. The objective of this study was to evaluate the effect of maternal hyperthyroidism on cardiac RAS components in pups during development. From gestational day nine (GD9), pregnant Wistar rats received thyroxine (T4, 12 mg/l in tap water; Hyper group) or vehicle (control group). Dams and pups were killed on GD18 and GD20. Serum concentrations of triiodothyronine (T3) and T4 were higher in the Hyper group than in the control group dams. Cardiac hypertrophy was observed in Hyper pups on GD20. Cardiac angiotensin-converting enzyme (ACE) activity was significantly lower in Hyper pups on both GD18 and GD20, but there was no difference in Ang I/Ang II levels. Ang II receptors expression was higher in the Hyper pup heart on GD18. Maternal hyperthyroidism is associated with alterations in fetal development and altered pattern of expression in RAS components, which in addition to cardiac hypertrophy observed on GD20 may represent an important predisposing factor to cardiovascular diseases in adult life.

Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

Directory of Open Access Journals (Sweden)

Abdelhalim Mohamed

2012-01-01

Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

The impact of traffic-flow patterns on air quality in urban street canyons

International Nuclear Information System (INIS)

Thaker, Prashant; Gokhale, Sharad

2016-01-01

We investigated the effect of different urban traffic-flow patterns on pollutant dispersion in different winds in a real asymmetric street canyon. Free-flow traffic causes more turbulence in the canyon facilitating more dispersion and a reduction in pedestrian level concentration. The comparison of with and without a vehicle-induced-turbulence revealed that when winds were perpendicular, the free-flow traffic reduced the concentration by 73% on the windward side with a minor increase of 17% on the leeward side, whereas for parallel winds, it reduced the concentration by 51% and 29%. The congested-flow traffic increased the concentrations on the leeward side by 47% when winds were perpendicular posing a higher risk to health, whereas reduced it by 17–42% for parallel winds. The urban air quality and public health can, therefore, be improved by improving the traffic-flow patterns in street canyons as vehicle-induced turbulence has been shown to contribute significantly to dispersion. - Highlights: • CFD is used to study impact of traffic-flow patterns on urban air quality. • Facilitating free-flow patterns induce more turbulence in street canyons. • Traffic-generated turbulence alters pollutant levels in urban street canyons. - This study investigates the effect of vehicle-induced-turbulence generated during free-flow traffic pattern in reduction of air pollutant concentrations in urban street canyons.

The N-Methyl-d-Aspartate Receptor Antagonist MK-801 Prevents Thallium-Induced Behavioral and Biochemical Alterations in the Rat Brain.

Science.gov (United States)

Osorio-Rico, Laura; Villeda-Hernández, Juana; Santamaría, Abel; Königsberg, Mina; Galván-Arzate, Sonia

2015-01-01

Thallium (Tl(+)) is a toxic heavy metal capable of increasing oxidative damage and disrupting antioxidant defense systems. Thallium invades the brain cells through potassium channels, increasing neuronal excitability, although until now the possible role of glutamatergic transmission in this event has not been investigated. Here, we explored the possible involvement of a glutamatergic component in the Tl(+)-induced toxicity through the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) in rats. The effects of MK-801 (1 mg/kg, intraperitoneally [ip]) on early (24 hours) motor alterations, lipid peroxidation, reduced glutathione (GSH) levels, and GSH peroxidase activity induced by Tl(+) acetate (32 mg/kg, ip) were evaluated in adult rats. MK-801 attenuated the Tl(+)-induced hyperactivity and lipid peroxidation in the rat striatum, hippocampus and midbrain, and produced mild effects on other end points. Our findings suggest that glutamatergic transmission via NMDA receptors might be involved in the Tl(+)-induced altered regional brain redox activity and motor performance in rats. © The Author(s) 2015.

Diabetes induces metabolic alterations in dental pulp.

Science.gov (United States)

Leite, Mariana Ferreira; Ganzerla, Emily; Marques, Márcia Martins; Nicolau, José

2008-10-01

Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

Chilling- and Freezing-Induced Alterations in Cytosine Methylation and Its Association with the Cold Tolerance of an Alpine Subnival Plant, Chorispora bungeana.

Directory of Open Access Journals (Sweden)

Yuan Song

Full Text Available Chilling (0-18°C and freezing (<0°C are two distinct types of cold stresses. Epigenetic regulation can play an important role in plant adaptation to abiotic stresses. However, it is not yet clear whether and how epigenetic modification (i.e., DNA methylation mediates the adaptation to cold stresses in nature (e.g., in alpine regions. Especially, whether the adaptation to chilling and freezing is involved in differential epigenetic regulations in plants is largely unknown. Chorispora bungeana is an alpine subnival plant that is distributed in the freeze-thaw tundra in Asia, where chilling and freezing frequently fluctuate daily (24 h. To disentangle how C. bungeana copes with these intricate cold stresses through epigenetic modifications, plants of C. bungeana were treated at 4°C (chilling and -4°C (freezing over five periods of time (0-24 h. Methylation-sensitive amplified fragment-length polymorphism markers were used to investigate the variation in DNA methylation of C. bungeana in response to chilling and freezing. It was found that the alterations in DNA methylation of C. bungeana largely occurred over the period of chilling and freezing. Moreover, chilling and freezing appeared to gradually induce distinct DNA methylation variations, as the treatment went on (e.g., after 12 h. Forty-three cold-induced polymorphic fragments were randomly selected and further analyzed, and three of the cloned fragments were homologous to genes encoding alcohol dehydrogenase, UDP-glucosyltransferase and polygalacturonase-inhibiting protein. These candidate genes verified the existence of different expressive patterns between chilling and freezing. Our results showed that C. bungeana responded to cold stresses rapidly through the alterations of DNA methylation, and that chilling and freezing induced different DNA methylation changes. Therefore, we conclude that epigenetic modifications can potentially serve as a rapid and flexible mechanism for C. bungeana

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

Science.gov (United States)

Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

2013-12-01

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

Directory of Open Access Journals (Sweden)

Darimont Christian

2004-08-01

Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

Regeneration patterns in boreal Scots pine glades linked to cold-induced photoinhibition

NARCIS (Netherlands)

Slot, M.; Wirth, C.; Schumacher, J.; Mohren, G.M.J.; Shibistova, O.; Lloyd, J.; Ensminger, I.

2005-01-01

Summary Regeneration patterns of Pinus sylvestris L. juveniles in central Siberian glades were studied in relation to cold-induced photoinhibition. Spatial distribution of seedlings in different height classes revealed higher seedling densities beneath the canopy than beyond the canopy, and

The Transcription Cofactor Swi6 of the Fusarium graminearum Is Involved in Fusarium Graminearum Virus 1 Infection-Induced Phenotypic Alterations

Directory of Open Access Journals (Sweden)

Moonil Son

2016-08-01

Full Text Available The transcription cofactor Swi6 plays important roles in regulating vegetative growth and meiosis in Saccharomyces cerevisiae. Functions of Swi6 ortholog were also characterized in Fusarium graminearum which is one of the devastating plant pathogenic fungi. Here, we report possible role of FgSwi6 in the interaction between F. graminearum and Fusarium graminearum virus 1 (FgV1 strain DK21. FgV1 perturbs biological characteristics of host fungi such as vegetative growth, sporulation, pigmentation, and reduction of the virulence (hypovirulence of its fungal host. To characterize function(s of FgSWI6 gene during FgV1 infection, targeted deletion, over-expression, and complementation mutants were generated and further infected successfully with FgV1. Deletion of FgSwi6 led to severe reduction of vegetative growth even aerial mycelia while over-expression did not affect any remarkable alteration of phenotype in virus-free isolates. Virus-infected (VI FgSWI6 deletion isolate exhibited completely delayed vegetative growth. However, VI FgSWI6 over-expression mutant grew faster than any other VI isolates. To verify whether these different growth patterns in VI isolates, viral RNA quantification was carried out using qRT-PCR. Surprisingly, viral RNA accumulations in VI isolates were similar regardless of introduced mutations. These results provide evidence that FgSWI6 might play important role(s in FgV1 induced phenotype alteration such as delayed vegetative growth.

Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

Directory of Open Access Journals (Sweden)

Abdulrahman K. Al-Asmari

2014-01-01

Full Text Available The potential effect of camel milk (CM against gentamicin (GM induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p., and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA and myeloperoxidase (MPO activity while the antioxidant enzymes like superoxide dismutase (SOD and glutathione s-transferase (GST activity decreased significantly (P≤0.05. Administration of CM significantly (P≤0.05 inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent.

Visual Learning Induces Changes in Resting-State fMRI Multivariate Pattern of Information.

Science.gov (United States)

Guidotti, Roberto; Del Gratta, Cosimo; Baldassarre, Antonello; Romani, Gian Luca; Corbetta, Maurizio

2015-07-08

When measured with functional magnetic resonance imaging (fMRI) in the resting state (R-fMRI), spontaneous activity is correlated between brain regions that are anatomically and functionally related. Learning and/or task performance can induce modulation of the resting synchronization between brain regions. Moreover, at the neuronal level spontaneous brain activity can replay patterns evoked by a previously presented stimulus. Here we test whether visual learning/task performance can induce a change in the patterns of coded information in R-fMRI signals consistent with a role of spontaneous activity in representing task-relevant information. Human subjects underwent R-fMRI before and after perceptual learning on a novel visual shape orientation discrimination task. Task-evoked fMRI patterns to trained versus novel stimuli were recorded after learning was completed, and before the second R-fMRI session. Using multivariate pattern analysis on task-evoked signals, we found patterns in several cortical regions, as follows: visual cortex, V3/V3A/V7; within the default mode network, precuneus, and inferior parietal lobule; and, within the dorsal attention network, intraparietal sulcus, which discriminated between trained and novel visual stimuli. The accuracy of classification was strongly correlated with behavioral performance. Next, we measured multivariate patterns in R-fMRI signals before and after learning. The frequency and similarity of resting states representing the task/visual stimuli states increased post-learning in the same cortical regions recruited by the task. These findings support a representational role of spontaneous brain activity. Copyright © 2015 the authors 0270-6474/15/359786-13$15.00/0.

Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.

Directory of Open Access Journals (Sweden)

Tracey A Martin

Full Text Available Methamphetamine (METH addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC. Our study investigated the effects of a non-toxic METH injection (20 mg/kg on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT, ATF2, and of the histone deacetylases (HDACs, HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf. In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck. Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac and lysine 18 (H3K18ac in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and

Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

Directory of Open Access Journals (Sweden)

Jarrar Bashir M

2011-09-01

Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

Photodynamic therapy induces antifibrotic alterations in primary human vocal fold fibroblasts.

Science.gov (United States)

Zhang, Chi; Wang, Jiajia; Chou, Adriana; Gong, Ting; Devine, Erin E; Jiang, Jack J

2018-04-18

Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. In vitro analysis from one human donor. Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method. Sublethal-dose PDT (SL-PDT) was used for the following experiments. Expression of genes related to vocal fold extracellular matrix formation was analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Effects of PDT on cell migration, collagen contraction, and transforming growth factor β-1 (TGF-β1)-induced myofibroblast differentiation were also analyzed. PDT affects the viability of VFFs in a dose-dependent manner. SL-PDT significantly changed the expression profile of VFFs with antifibrotic effects. It also inhibited cell migration, reduced collagen contraction, and reversed the fibroblast-myofibroblast differentiation induced by TGF-β1. SL-PDT induces antifibrotic alterations in VFFs. This could explain the low incidence of vocal fold scar associated with PDT. Moreover, PDT may be useful in treating existing vocal fold scars. Further studies should focus on the in vivo effect of PDT on vocal fold wound healing and scar remodeling. NA Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

Science.gov (United States)

Thomas, J; Nores, W L; Pariser, R

1993-07-01

The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

Proteome alteration induced by hTERT transfection of human fibroblast cells.

Science.gov (United States)

Mazzucchelli, Gabriel D; Gabelica, Valérie; Smargiasso, Nicolas; Fléron, Maximilien; Ashimwe, Wilson; Rosu, Frédéric; De Pauw-Gillet, Marie-Claire; Riou, Jean-François; De Pauw, Edwin

2008-04-17

Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT) gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38). Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV) and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis) analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest that telomerase expression enhances natural cell repair

Proteome alteration induced by hTERT transfection of human fibroblast cells

Directory of Open Access Journals (Sweden)

Riou Jean-François

2008-04-01

Full Text Available Abstract Background Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38. Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. Results 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. Conclusion We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest

Preliminary study about frequencies of unstable chromosome alterations induced by gamma beam and neutron-gamma mixed field

International Nuclear Information System (INIS)

Mendes, Mariana E.; Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide

2011-01-01

The estimate on approximate dose in exposed individual can be made through conventional cytogenetic analysis of dicentric, this technique has been used to support physical dosimetry. It is important to estimate the absorbed dose in case of accidents with the aim of developing an appropriate treatment and biological dosimetry can be very useful in case where the dosimetry is unavailable. Exposure to gamma and neutron radiation leads to the same biological effects such as chromosomal alterations and cancer. However, neutrons cause more genetic damage, such as mutation or more structural damage, such as chromosome alterations. The aim of research is to compare frequencies of unstable chromosome alterations induced by a gamma beam with those from neutron-gamma mixed field. Two blood samples were obtained from one healthy donor and irradiated at different sources. The first sample was exposed to mixed field neutron-gamma sources 241 AmBe at the Neutron Calibration Laboratory (NCL - CRCN/NE - PE - Brazil) and the second one was exposed to 137 Cs gamma rays at 137 Cs Laboratory (CRCN/NE - PE - Brazil), both exposures resulting in an absorbed dose of 0.66Gy. Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. These preliminary results showed a similarity in associated dicentrics frequency per cell (0.041 and 0.048) after 137 Cs and 241 AmBe sources irradiations, respectively. However, it was not observed centric rings frequency per cell (0.0 and 0.027). This study will be continue to verify the frequencies of unstable chromosome alterations induced by only gamma beam and neutron-gamma mixed field. (author)

Preliminary study about frequencies of unstable chromosome alterations induced by gamma beam and neutron-gamma mixed field

Energy Technology Data Exchange (ETDEWEB)

Mendes, Mariana E.; Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide [Universidade Federal de Pernanmbuco (CCB/UFPE), Recife, PE (Brazil). Centro de Ciencias Biologicas. Dept. de Genetica

2011-07-01

The estimate on approximate dose in exposed individual can be made through conventional cytogenetic analysis of dicentric, this technique has been used to support physical dosimetry. It is important to estimate the absorbed dose in case of accidents with the aim of developing an appropriate treatment and biological dosimetry can be very useful in case where the dosimetry is unavailable. Exposure to gamma and neutron radiation leads to the same biological effects such as chromosomal alterations and cancer. However, neutrons cause more genetic damage, such as mutation or more structural damage, such as chromosome alterations. The aim of research is to compare frequencies of unstable chromosome alterations induced by a gamma beam with those from neutron-gamma mixed field. Two blood samples were obtained from one healthy donor and irradiated at different sources. The first sample was exposed to mixed field neutron-gamma sources {sup 241}AmBe at the Neutron Calibration Laboratory (NCL - CRCN/NE - PE - Brazil) and the second one was exposed to {sup 137}Cs gamma rays at {sup 137}Cs Laboratory (CRCN/NE - PE - Brazil), both exposures resulting in an absorbed dose of 0.66Gy. Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. These preliminary results showed a similarity in associated dicentrics frequency per cell (0.041 and 0.048) after {sup 137}Cs and {sup 241}AmBe sources irradiations, respectively. However, it was not observed centric rings frequency per cell (0.0 and 0.027). This study will be continue to verify the frequencies of unstable chromosome alterations induced by only gamma beam and neutron-gamma mixed field. (author)

Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization

Directory of Open Access Journals (Sweden)

Felipe Vidal

2017-12-01

Full Text Available One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4 in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25 and polyethylene glycol (PPEG25. G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.

Kinetics of radiation-induced structural alterations in electron-irradiated polymer-based composites

International Nuclear Information System (INIS)

Zaikin, Yu.A.; Potanin, A.S.; Koztaeva, U.P.

2002-01-01

Complete text of publication follows. In our previous studies measurements of internal friction temperature dependence were used for characterization of thermally activated and radiation-induced structural evolution in different types of polymer-based composites. This paper supplements these measurements with kinetic studies of internal friction (IF) parameters and EPR signals in a glass-cloth epoxy-filled laminate ST-ETF after electron irradiation up to doses of 1-10 MGy. Experiment have shown that the lifetime of free radicals in this composite considerably exceeds the characteristic time of molecular structural rearrangement due to scission and cross-linking after irradiation, as determined from IF measurements. This result is explained by slow proceeding of sterically hindered disproportionation reactions that stabilize the end groups of the macro-chain disrupt during irradiation and finally fix the act of scission. A mathematical model is formulated for description of structural evolution and alterations of IF parameters in polymer-based composites during and after electron irradiation. The description is based on the track model of radiation damage in polymers and phenomenological theory of radiation-induced structural transformations. General description does not give details of radiation-chemical conversion in different structural components of composites but indicates the direction of their structural evolution. In the model considered a composite material was divided into three parts (binder, filler, and a boundary layer). It was supposed that after primary distribution of radiation energy radiation-chemical conversion proceeds independently in each of these regions. It was also suggested that all the radical reactions were of the second order. On the example of glass-cloth laminate ST-ETF it is shown that this model allows to describe alterations in composite structural characteristics during irradiation and in the course of their self-organization after

Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

Science.gov (United States)

Bridges, Robert S.

2015-01-01

The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

Femtosecond self-reconfiguration of laser-induced plasma patterns in dielectrics

Science.gov (United States)

Déziel, Jean-Luc; Dubé, Louis J.; Messaddeq, Sandra H.; Messaddeq, Younès; Varin, Charles

2018-05-01

Laser-induced modification of transparent solids by intense femtosecond laser pulses allows fast integration of nanophotonic and nanofluidic devices with controlled optical properties. Experimental observations suggest that the local and dynamic nature of the interactions between light and the transient plasma plays an important role during fabrication. Current analytical models neglect these aspects and offer limited coverage of nanograting formation on dielectric surfaces. In this paper, we present a self-consistent dynamic treatment of the plasma buildup and its interaction with light within a three-dimensional electromagnetic framework. The main finding of this work is that local light-plasma interactions are responsible for the reorientation of laser-induced periodic plasma patterns with respect to the incident light polarization, when a certain energy density threshold is reached. Plasma reconfiguration occurs within a single laser pulse, on a femtosecond time scale. Moreover, we show that the reconfigured subwavelength plasma structures actually grow into the bulk of the sample, which agrees with the experimental observations of self-organized volume nanogratings. We find that mode coupling of the incident and transversely scattered light with the periodic plasma structures is sufficient to initiate the growth and self-organization of the pattern inside the medium with a characteristic half-wavelength periodicity.

Influence of ion bombardment induced patterning of exchange bias in pinned artificial ferrimagnets on the interlayer exchange coupling

Energy Technology Data Exchange (ETDEWEB)

Schmalhorst, Jan; Reiss, Guenter; Hoenik, V. [Thin Films and Nanostructures, Department of Physics, Univ. Bielefeld (Germany); Weis, Tanja; Engel, Dieter; Ehresmann, Arno [Institute of Physics and Center for Interdisciplinary Nanostructure Science and Technology, Kassel Univ. (Germany)

2007-07-01

Artificial ferrimagnets (AFi) have many applications as, e.g., pinned reference electrodes in magnetic tunnel junctions. It is known that the application of ion bombardment induced magnetic patterning with He ions on a single layer reference electrode of magnetic tunnel junctions is possible. For some applications a combination of ion bombardment induced magnetic patterning and artificial ferrimagnets as a reference electrode is desirable. The effect of ion bombardment induced magnetic patterning on pinned artificial ferrimagnets with a Ru interlayer which is frequently used in magnetic tunnel junctions as well as pinned AFis with a Cu interlayer has been tested. Special attention has been given to the question whether the antiferromagnetic interlayer exchange coupling can withstand the ion dose necessary to turn the exchange bias.

Re-examine tumor-induced alterations in hemodynamic responses of BOLD fMRI. Implications in presurgical brain mapping

International Nuclear Information System (INIS)

Wang, Liya; Ali, Shazia; Fa, Tianning; Mao, Hui; Dandan, Chen; Olson, Jeffrey

2012-01-01

Background: Blood oxygenation level dependent (BOLD) fMRI is used for presurgical functional mapping of brain tumor patients. Abnormal tumor blood supply may affect hemodynamic responses and BOLD fMRI signals. Purpose: To perform a multivariate and quantitative investigation of the effect of brain tumors on the hemodynamic responses and its impact on BOLD MRI signal time course, data analysis in order to better understand tumor-induced alterations in hemodynamic responses, and accurately mapping cortical regions in brain tumor patients. Material and Methods: BOLD fMRI data from 42 glioma patients who underwent presurgical mapping of the primary motor cortex (PMC) with a block designed finger tapping paradigm were analyzed, retrospectively. Cases were divided into high grade (n = 24) and low grade (n = 18) groups based on pathology. The tumor volume and distance to the activated PMCs were measured. BOLD signal time courses from selected regions of interest (ROIs) in the PMCs of tumor affected and contralateral unaffected hemispheres were obtained from each patient. Tumor-induced changes of BOLD signal intensity and time to peak (TTP) of BOLD signal time courses were analyzed statistically. Results: The BOLD signal intensity and TTP in the tumor-affected PMCs are altered when compared to that of the unaffected hemisphere. The average BOLD signal level is statistically significant lower in the affected PMCs. The average TTP in the affected PMCs is shorter in the high grade group, but longer in the low grade tumor group compared to the contralateral unaffected hemisphere. Degrees of alterations in BOLD signal time courses are related to both the distance to activated foci and tumor volume with the stronger effect in tumor distance to activated PMC. Conclusion: Alterations in BOLD signal time courses are strongly related to the tumor grade, the tumor volume, and the distance to the activated foci. Such alterations may impair accurate mapping of tumor-affected functional

Data set of Aspergillus flavus induced alterations in tear proteome: Understanding the pathogen-induced host response to fungal infection

Directory of Open Access Journals (Sweden)

Jeyalakshmi Kandhavelu

2016-12-01

Full Text Available Fungal keratitis is one of the leading causes of blindness in the tropical countries affecting individuals in their most productive age. The host immune response during this infection is poorly understood. We carried out comparative tear proteome analysis of Aspergillus flavus keratitis patients and uninfected controls. Proteome was separated into glycosylated and non-glycosylated fractions using lectin column chromatography before mass spectrometry. The data revealed the major processes activated in the human host in response to fungal infection and reflected in the tear. Extended analysis of this dataset presented here complements the research article entitled “Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection [1]” (Jeyalakhsmi Kandhavelu, Naveen Luke Demonte, Venkatesh Prajna Namperumalsamy, Lalitha Prajna, Chitra Thangavel, Jeya Maheshwari Jayapal, Dharmalingam Kuppamuthu, 2016. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE:PXD003825.

Tropical deforestation alters hummingbird movement patterns

Science.gov (United States)

Hadley, Adam S.; Betts, Matthew G.

2009-01-01

Reduced pollination success, as a function of habitat loss and fragmentation, appears to be a global phenomenon. Disruption of pollinator movement is one hypothesis put forward to explain this pattern in pollen limitation. However, the small size of pollinators makes them very difficult to track; thus, knowledge of their movements is largely speculative. Using tiny radio transmitters (0.25 g), we translocated a generalist tropical ‘trap-lining’ hummingbird, the green hermit (Phaethornis guy), across agricultural and forested landscapes to test the hypothesis that movement is influenced by patterns of deforestation. Although, we found no difference in homing times between landscape types, return paths were on average 459±144 m (±s.e.) more direct in forested than agricultural landscapes. In addition, movement paths in agricultural landscapes contained 36±4 per cent more forest than the most direct route. Our findings suggest that this species can circumvent agricultural matrix to move among forest patches. Nevertheless, it is clear that movement of even a highly mobile species is strongly influenced by landscape disturbance. Maintaining landscape connectivity with forest corridors may be important for enhancing movement, and thus in facilitating pollen transfer. PMID:19158031

Global metabolomic responses of Nitrosomonas europaea 19718 to cold stress and altered ammonia feeding patterns

KAUST Repository

Lu, Huijie; Ulanov, Alexander V.; Nobu, Masaru; Liu, Wen-Tso

2015-01-01

© 2015 Springer-Verlag Berlin Heidelberg The model ammonia-oxidizing bacterium Nitrosomonas europaea represents one of the environmentally and biotechnologically significant microorganisms. Genome-based studies over the last decade have led to many intriguing discoveries about its cellular biochemistry and physiology. However, knowledge regarding the regulation of overall metabolic routes in response to various environmental stresses is limited due to a lack of comprehensive, time-resolved metabolomic analyses. In this study, gas chromatography–mass spectrometry (GC-MS)-based metabolic profiling was performed to characterize the temporal variations of N. europaea 19718 intercellular metabolites in response to varied temperature (23 and 10 °C) and ammonia feeding patterns (shock loading and continuous feeding of 20 mg N/L). Approximately 87 metabolites were successfully identified and mapped to the existing pathways of N. europaea 19718, allowing interpretation of the influence of temperature and feeding pattern on metabolite levels. In general, varied temperature had a more profound influence on the overall metabolism than varied feeding patterns. Total extracellular metabolite concentrations (relative to internal standards and normalized to biomass weight) were lower under cold stress and shock loading conditions compared with the control (continuous feeding at 23 °C). Cold stress caused the widespread downregulation of metabolites involved in central carbon metabolism, amino acid, and lipid synthesis (e.g., malonic acid, succinic acid, putrescine, and phosphonolpyruvate). Metabolites that showed differences under varied feeding patterns were mainly involved in nucleotide acid, amino acid, and lipid metabolism (e.g., adenine, uracil, and spermidine). This study highlighted the roles of central carbon and nitrogen metabolism in countering cold stress and altered ammonia availability. In addition, transcriptomic, proteomic, and metabolomic data from three

Light at night alters daily patterns of cortisol and clock proteins in female Siberian hamsters.

Science.gov (United States)

Bedrosian, T A; Galan, A; Vaughn, C A; Weil, Z M; Nelson, R J

2013-06-01

Humans and other organisms have adapted to a 24-h solar cycle in response to life on Earth. The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length. To successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm of approximately 24 h in length. These rhythms arise from hierarchally-coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression. From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge. These circadian rhythms in physiology and behaviour can be organised by a variety of cues, although they are most potently entrained by light. In recent history, there has been a major change from naturally-occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting. Virtually every individual living in an industrialised country experiences light at night (LAN) but, despite its prevalence, the biological effects of such unnatural lighting have not been fully considered. Using female Siberian hamsters (Phodopus sungorus), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations and brain expression of circadian clock proteins (i.e. PER1, PER2, BMAL1). Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the suprachiasmatic nucleus and hippocampus were altered. These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology. © 2013 British Society for Neuroendocrinology.

Global metabolomic responses of Nitrosomonas europaea 19718 to cold stress and altered ammonia feeding patterns

KAUST Repository

Lu, Huijie

2015-11-05

© 2015 Springer-Verlag Berlin Heidelberg The model ammonia-oxidizing bacterium Nitrosomonas europaea represents one of the environmentally and biotechnologically significant microorganisms. Genome-based studies over the last decade have led to many intriguing discoveries about its cellular biochemistry and physiology. However, knowledge regarding the regulation of overall metabolic routes in response to various environmental stresses is limited due to a lack of comprehensive, time-resolved metabolomic analyses. In this study, gas chromatography–mass spectrometry (GC-MS)-based metabolic profiling was performed to characterize the temporal variations of N. europaea 19718 intercellular metabolites in response to varied temperature (23 and 10 °C) and ammonia feeding patterns (shock loading and continuous feeding of 20 mg N/L). Approximately 87 metabolites were successfully identified and mapped to the existing pathways of N. europaea 19718, allowing interpretation of the influence of temperature and feeding pattern on metabolite levels. In general, varied temperature had a more profound influence on the overall metabolism than varied feeding patterns. Total extracellular metabolite concentrations (relative to internal standards and normalized to biomass weight) were lower under cold stress and shock loading conditions compared with the control (continuous feeding at 23 °C). Cold stress caused the widespread downregulation of metabolites involved in central carbon metabolism, amino acid, and lipid synthesis (e.g., malonic acid, succinic acid, putrescine, and phosphonolpyruvate). Metabolites that showed differences under varied feeding patterns were mainly involved in nucleotide acid, amino acid, and lipid metabolism (e.g., adenine, uracil, and spermidine). This study highlighted the roles of central carbon and nitrogen metabolism in countering cold stress and altered ammonia availability. In addition, transcriptomic, proteomic, and metabolomic data from three

Global metabolomic responses of Nitrosomonas europaea 19718 to cold stress and altered ammonia feeding patterns.

Science.gov (United States)

Lu, Huijie; Ulanov, Alexander V; Nobu, Masaru; Liu, Wen-Tso

2016-02-01

The model ammonia-oxidizing bacterium Nitrosomonas europaea represents one of the environmentally and biotechnologically significant microorganisms. Genome-based studies over the last decade have led to many intriguing discoveries about its cellular biochemistry and physiology. However, knowledge regarding the regulation of overall metabolic routes in response to various environmental stresses is limited due to a lack of comprehensive, time-resolved metabolomic analyses. In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling was performed to characterize the temporal variations of N. europaea 19718 intercellular metabolites in response to varied temperature (23 and 10 °C) and ammonia feeding patterns (shock loading and continuous feeding of 20 mg N/L). Approximately 87 metabolites were successfully identified and mapped to the existing pathways of N. europaea 19718, allowing interpretation of the influence of temperature and feeding pattern on metabolite levels. In general, varied temperature had a more profound influence on the overall metabolism than varied feeding patterns. Total extracellular metabolite concentrations (relative to internal standards and normalized to biomass weight) were lower under cold stress and shock loading conditions compared with the control (continuous feeding at 23 °C). Cold stress caused the widespread downregulation of metabolites involved in central carbon metabolism, amino acid, and lipid synthesis (e.g., malonic acid, succinic acid, putrescine, and phosphonolpyruvate). Metabolites that showed differences under varied feeding patterns were mainly involved in nucleotide acid, amino acid, and lipid metabolism (e.g., adenine, uracil, and spermidine). This study highlighted the roles of central carbon and nitrogen metabolism in countering cold stress and altered ammonia availability. In addition, transcriptomic, proteomic, and metabolomic data from three studies on N. europaea were compared to achieve a

Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

Science.gov (United States)

Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

2016-03-01

Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

Directory of Open Access Journals (Sweden)

Alya Annabi

2015-11-01

Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

DEFF Research Database (Denmark)

Genster, Ninette; Østrup, Olga; Schjalm, Camilla

2017-01-01

. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

Gene alterations in radiation-induced F344 rat lung tumors

International Nuclear Information System (INIS)

Kelly, G.; Hahn, F.F.

1994-01-01

The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

Science.gov (United States)

Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

1995-02-06

EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

Exploring patterns of alteration in Alzheimer’s disease brain networks: a combined structural and functional connectomics analysis

Directory of Open Access Journals (Sweden)

Fulvia Palesi

2016-09-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the disconnection syndrome hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks in patients affected by AD and mild cognitive impairment (MCI. However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC. In the default mode network (DMN, that was the most affected, axonal loss and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN, disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN, neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI but also with subcortical alterations (revealed by diffusion MRI that extend beyond the areas primarily damaged by neurodegeneration, towards the support of an emerging concept of AD as a

Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

Science.gov (United States)

Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

2018-07-04

Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

6-OHDA induced calcium influx through N-type calcium channel alters membrane properties via PKA pathway in substantia nigra pars compacta dopaminergic neurons.

Science.gov (United States)

Qu, Liang; Wang, Yuan; Zhang, Hai-Tao; Li, Nan; Wang, Qiang; Yang, Qian; Gao, Guo-Dong; Wang, Xue-Lian

2014-07-11

Voltage gated calcium channels (VGCC) are sensitive to oxidative stress, and their activation or inactivation can impact cell death. Although these channels have been extensively studied in expression systems, their role in the brain, particularly in the substantia nigra pars compacta (SNc), remain controversial. In this study, we assessed 6-hydroxydopamine (6-OHDA) induced transformation of firing pattern and functional changes of calcium channels in SNc dopaminergic neurons. Application of 6-OHDA (0.5-2mM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca(2+)]i) rise. In voltage clamp, ω-conotoxin-sensitive Ca(2+) current modulation mediated by 6-OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA modulated Ca(2+) currents through PKA pathway. These results provided evidence for the potential role of VGCCs and PKA involved in oxidative stress in degeneration of SNc neurons in Parkinson's disease (PD). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Spatial pattern formation induced by Gaussian white noise.

Science.gov (United States)

Scarsoglio, Stefania; Laio, Francesco; D'Odorico, Paolo; Ridolfi, Luca

2011-02-01

The ability of Gaussian noise to induce ordered states in dynamical systems is here presented in an overview of the main stochastic mechanisms able to generate spatial patterns. These mechanisms involve: (i) a deterministic local dynamics term, accounting for the local rate of variation of the field variable, (ii) a noise component (additive or multiplicative) accounting for the unavoidable environmental disturbances, and (iii) a linear spatial coupling component, which provides spatial coherence and takes into account diffusion mechanisms. We investigate these dynamics using analytical tools, such as mean-field theory, linear stability analysis and structure function analysis, and use numerical simulations to confirm these analytical results. Copyright © 2010 Elsevier Inc. All rights reserved.

Strain-typical patterns of pregnancy-induced nestbuilding in mice: maternal and experiential influences.

Science.gov (United States)

Broida, J; Svare, B

1982-07-01

Pregnant C57BL/6J mice incorporate less material into maternal nests and build fewer fully enclosed nests than do pregnant DBA/2J mice. These strain differences are not ameliorated by additional reproductive experience since multiparous animals also exhibit a similar pattern. Reciprocally-crossed hybrid females exhibit DBA-like levels of pregnancy-induced nestbuilding and cross-fostered C57BL and DBA females retain the phenotype of their strain. Experiential and maternal environmental factors apparently are not responsible for strain differences in pregnancy-induced nestbuilding. Differences in ovarian function and/or central neural tissue sensitivity to ovarian hormones may modulate strain differences in pregnancy-induced nestbuilding.

Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells.

Science.gov (United States)

Liu, Qian; Sun, Shanquan; Yu, Wei; Jiang, Jin; Zhuo, Fei; Qiu, Guoping; Xu, Shiye; Jiang, Xuli

2015-04-01

Long non-coding RNAs (lncRNAs), a recently discovered class of non-coding genes, are transcribed throughout the genome. Emerging evidence suggests that lncRNAs may be involved in modulating various aspects of tumor biology, including regulating gene activity in response to external stimuli or DNA damage. No data are available regarding the expression of lncRNAs during genotoxic stress-induced apoptosis and/or necrosis in human glioma cells. In this study, we detected a change in the expression of specific candidate lncRNAs (neat1, GAS5, TUG1, BC200, Malat1, MEG3, MIR155HG, PAR5, and ST7OT1) during DNA damage-induced apoptosis in human glioma cell lines (U251 and U87) using doxorubicin (DOX) and resveratrol (RES). We also detected the expression pattern of these lncRNAs in human glioma cell lines under necrosis induced using an increased dose of DOX. Our results reveal that the lncRNA expression patterns are distinct between genotoxic stress-induced apoptosis and necrosis in human glioma cells. The sets of lncRNA expressed during genotoxic stress-induced apoptosis were DNA-damaging agent-specific. Generally, MEG3 and ST7OT1 are up-regulated in both cell lines under apoptosis induced using both agents. The induction of GAS5 is only clearly detected during DOX-induced apoptosis, whereas the up-regulation of neat1 and MIR155HG is only found during RES-induced apoptosis in both cell lines. However, TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. In conclusion, our findings suggest that the distinct regulation of lncRNAs may possibly involve in the process of cellular defense against genotoxic agents.

Altered motor unit discharge patterns in paretic muscles of stroke survivors assessed using surface electromyography

Science.gov (United States)

Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

2016-08-01

Objective. Hemispheric stroke survivors often show impairments in voluntary muscle activation. One potential source of these impairments could come from altered control of muscle, via disrupted motor unit (MU) firing patterns. In this study, we sought to determine whether MU firing patterns are modified on the affected side of stroke survivors, as compared with the analogous contralateral muscle. Approach. Using a novel surface electromyogram (EMG) sensor array, coupled with advanced template recognition software (dEMG) we recorded surface EMG signals over the first dorsal interosseous (FDI) muscle on both paretic and contralateral sides. Recordings were made as stroke survivors produced isometric index finger abductions over a large force range (20%-60% of maximum). Utilizing the dEMG algorithm, MU firing rates, recruitment thresholds, and action potential amplitudes were estimated for concurrently active MUs in each trial. Main results. Our results reveal significant changes in the firing rate patterns in paretic FDI muscle, in that the discharge rates, characterized in relation to recruitment force threshold and to MU size, were less clearly correlated with recruitment force than in contralateral FDI muscles. Firing rates in the affected muscle also did not modulate systematically with the level of voluntary muscle contraction, as would be expected in intact muscles. These disturbances in firing properties also correlated closely with the impairment of muscle force generation. Significance. Our results provide strong evidence of disruptions in MU firing behavior in paretic muscles after a hemispheric stroke, suggesting that modified control of the spinal motoneuron pool could be a contributing factor to muscular weakness in stroke survivors.

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

Energy Technology Data Exchange (ETDEWEB)

Hotchkiss, J A; Portereiko, J V; Harkema, J R

1988-12-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

1988-01-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

Patterns of gravity induced aggregate migration during casting of fluid concretes

Energy Technology Data Exchange (ETDEWEB)

Spangenberg, J. [Department of Mechanical Engineering, Technical University of Denmark (DTU) (Denmark); Roussel, N., E-mail: Nicolas.roussel@lcpc.fr [Universite Paris Est, Laboratoire Central des Ponts et Chaussees (LCPC) (France); Hattel, J.H. [Department of Mechanical Engineering, Technical University of Denmark (DTU) (Denmark); Sarmiento, E.V.; Zirgulis, G. [Department of Structural Engineering, Norwegian University of Science and Technology (NTNU) (Norway); Geiker, M.R. [Department of Structural Engineering, Norwegian University of Science and Technology (NTNU) (Norway); Department of Civil Engineering, Technical University of Denmark (DTU) (Denmark)

2012-12-15

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration.

Patterns of gravity induced aggregate migration during casting of fluid concretes

International Nuclear Information System (INIS)

Spangenberg, J.; Roussel, N.; Hattel, J.H.; Sarmiento, E.V.; Zirgulis, G.; Geiker, M.R.

2012-01-01

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration.

Hemopathologic consequences of protracted gamma irradiation: alterations in granulocyte reserves and granulocyte mobilization

International Nuclear Information System (INIS)

Seed, T.M.; Cullen, S.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.

1980-01-01

Aplastic anemia and myelogenous leukemia are prominent pathologic effects in beagles exposed to continuous, daily, low-dose gamma irradiation. In the present work, granulocyte reserves and related mobilization functions have been sequentially assessed by the endotoxin stress assay during the preclinical and clinical phases of these hemopoietic disorders. Characteristic patterns of granulocyte reserve mobilization are described that reflect given stages of pathologic progression. For radiation-induced leukemia, a five-stage pattern has been proposed. In contrast, a simple pattern of progressive, time-dependent contraction of granulocyte reserves and mobilization capacity was noted in the development of terminal aplastic anemia. Early preclinical phases of radiation-induced leukemia appear to involve an extensive depletion of the granulocyte reserves (phase I) during the first approx. 200 days of exposure followed by a partial renewal of the reserves and associated mobilization functions between approx. 200 and 400 days (phase II). Sustained, subnormal granulocyte mobilizations (phase III) following endotoxin stress typify the responses of dogs during the intermediate phase, whereas late preclinical, preleukemic stages (phase IV) are characterized by a further expansion of the reserves and in the mobilization capacities, particularly of the less mature granulocytes. Such late alterations in the pattern of granulocyte mobilization, together with other noted cellular aberrancies in the peripheral blood and marrow, appear to indicate leukemia (phase V) onset

Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by 60Co

International Nuclear Information System (INIS)

Tavakoli, H.; Manoochehri, M.; Mosalla, S. M. M.; Ghafori, M.; Karimi, A. A.

2013-01-01

Growth arrest DNA damage-inducible 45a gene (Gadd45a) and immediate early response gene 5 (Ier5) have been emphasised as ideal radiation bio-markers in several reports. However, some aspects of radiation-induced transcriptional alterations of these genes are unknown. In this study, gender-dependency and dose-dependency as two factors that may affect radiation induced transcription of Gadd45a and Ier5 genes were investigated. Human lymphocyte cells from six healthy voluntary blood donors (three women and three men) were irradiated in vitro with doses of 0.5-4.0 Gy from a 60 Co source and RNA isolated 4 h later using the High Pure RNA Isolation Kit. Dose and gender dependency of radiation-induced transcriptional alterations of Gadd45a and Ier5 genes were studied by quantitative real-time polymerase chain reaction. The results showed that as a whole, Gadd45a and Ier5 gave responses to gamma rays, while the responses were independent of radiation doses. Therefore, regardless of radiation dose, Gadd45a and Ier5 can be considered potential radiation bio-markers. Besides, although radiation-induced transcriptional alterations of Gadd45a in female and male lymphocyte samples were insignificant at 0.5 Gy, at other doses, their quantities in female samples were at a significantly higher level than in male samples. Radiation induced transcription of Ier5 of females samples had a reduction in comparison with male samples at 1 and 2 Gy, but at doses of 0.5 and 4 Gy, females were significantly more susceptible to radiation-induced transcriptional alteration of Ier5. (authors)

Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

Energy Technology Data Exchange (ETDEWEB)

Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

2012-06-29

Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

Mapping transient hyperventilation induced alterations with estimates of the multi-scale dynamics of BOLD signal.

Directory of Open Access Journals (Sweden)

Vesa J Kiviniemi

2009-07-01

Full Text Available Temporal blood oxygen level dependent (BOLD contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD trends of the form 1/f α. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal.

Science.gov (United States)

Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

2009-01-01

Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/f(alpha). Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant alpha, fractal dimension D(f), and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The alpha was able to differentiate also blood vessels from grey matter changes. D(f) was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

Proliferative response of the murine esophageal epithelium to radiation: Modification by food consumption patterns

International Nuclear Information System (INIS)

Burholt, D.R.

1985-01-01

The single layer of proliferative epithelial cells of the murine esophagus undergoes a sequence of damage and recovery following cytotoxic insult. The modification of both damage and proliferative recovery by the alteration of animal eating patterns was investigated following thoracic field irradiation through the determination of /sup 3/H-TdR incorporation into the esophagus along with selective counting of labeled nuclei and mitotic figures. Initial radiation-induced damage, as determined by /sup 3/H-TdR incorporation suppression and mitotic delay, is under normal conditions dependent on the time of day of treatment. This circadian sensitivity may be altered by changing the eating pattern of the animal. The proliferative recovery following single dose irradiation is also dependent on food consumption patterns: fasting immediately following treatment and then refeeding 2 days later results in a more rapid proliferative recovery than observed under control eating conditions, while reduced food consumption during the period of proliferative hyperplasia reduces the extent of recovery. During multifraction radiation schedules both the damage produced by a subsequent dose and recovery capacity are influenced by the food consumption pattern between fractions

Origin of convex tetrads in rare earth element patterns of hydrothermally altered siliceous igneous rocks from the Zinnwald Sn W deposit, Germany

Science.gov (United States)

Monecke, T.; Dulski, P.; Kempe, U.

2007-01-01

The chondrite-normalized rare earth element (REE) patterns of whole rock samples from evolved granitic systems hosting rare metal deposits sometimes show a split into four consecutive curved segments, referred to as tetrads. In the present contribution, a rigorous statistical method is proposed that can be used to test whether geological significance should be attributed to tetrads that are only of limited size. The method involves a detailed evaluation of element and sample specific random and systematic errors that are constrained on the basis of independent repeated preparations and analyses of sample and reference materials. Application of the proposed method to samples from the granite-hosted Zinnwald Sn-W deposit, Germany, revealed that at least two tetrads in normalized whole rock REE patterns have to be analytically significant to rule out that fractional crystallization led to the unusual behavior of the REEs. Based on the analysis of altered albite granite and greisen samples from the endocontact of the Zinnwald granite massif, it is demonstrated that the lanthanide tetrad effect is responsible for the formation of the convex tetrads. Geological and petrological evidence suggests that the tetrads in the samples developed prior to greisenization and related cassiterite precipitation. In contrast to the endocontact samples, the rhyolitic wall rocks are typified by normalized REE patterns having tetrads that are variable in size and frequently close to the limit of analytical significance. The sizes of the tetrads apparently correlate with the intensity of albitization, but show no relation to subsequent alteration processes including greisenization and low-temperature argillization. This observation proves that curved segments in normalized whole rock REE patterns can be introduced during hydrothermal fluid-rock interaction.

Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

Directory of Open Access Journals (Sweden)

Rodrigo eIturriaga

2014-12-01

Full Text Available The carotid body (CB plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure and obstructive sleep apnea (OSA. Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH, a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation.

Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

Science.gov (United States)

Iturriaga, Rodrigo; Andrade, David C.; Del Rio, Rodrigo

2014-01-01

The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation. PMID:25520668

Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms.

Directory of Open Access Journals (Sweden)

Rebecca E Haddock

Full Text Available BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat. Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca/IK(Ca inhibition; with such activity being impaired in obesity. SK(Ca-IK(Ca activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine (CyPPA and 1-ethyl-2-benzimidazolinone (1-EBIO, respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca distribution and elevated expression. In contrast, the SK(Ca-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir and Na(+/K(+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K

Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

Science.gov (United States)

Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

2013-11-15

Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

Self-Organized Patterns Induced by Neimark-Sacker, Flip and Turing Bifurcations in a Discrete Predator-Prey Model with Lesie-Gower Functional Response

Directory of Open Access Journals (Sweden)

Feifan Zhang

2017-06-01

Full Text Available The formation of self-organized patterns in predator-prey models has been a very hot topic recently. The dynamics of these models, bifurcations and pattern formations are so complex that studies are urgently needed. In this research, we transformed a continuous predator-prey model with Lesie-Gower functional response into a discrete model. Fixed points and stability analyses were studied. Around the stable fixed point, bifurcation analyses including: flip, Neimark-Sacker and Turing bifurcation were done and bifurcation conditions were obtained. Based on these bifurcation conditions, parameters values were selected to carry out numerical simulations on pattern formation. The simulation results showed that Neimark-Sacker bifurcation induced spots, spirals and transitional patterns from spots to spirals. Turing bifurcation induced labyrinth patterns and spirals coupled with mosaic patterns, while flip bifurcation induced many irregular complex patterns. Compared with former studies on continuous predator-prey model with Lesie-Gower functional response, our research on the discrete model demonstrated more complex dynamics and varieties of self-organized patterns.

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

Science.gov (United States)

Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

2015-08-01

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

Effects of interleukins 2 and 12 on TBT-induced alterations of MAP kinases p38 and p44/42 in human natural killer cells.

Science.gov (United States)

Aluoch, Aloice O; Whalen, Margaret M

2006-01-01

NK cells are lymphocytes in the non-adaptive immune system that protect the body against intracellular pathogens and eliminate tumor cells. Tributyltin (TBT) is a toxic chemical that has been detected in human foods as well as in human blood. The role of TBT in immunosuppression has been described, including inhibition of the human NK-cell cytotoxic function. Previous studies indicated that exposure of NK cells to TBT for 1 h induced progressive and irreversible inhibition of cytotoxic function. However, it was found that if NK cells were incubated in TBT-free media with either IL-2 or IL-12, loss of cytotoxic function was prevented/reversed within 24 h. Molecular studies established that loss of cytotoxic function is accompanied by alteration of MAP kinases (MAPKs) p38 and p44/42 phosphorylation. This study examined whether interleukin-mediated recovery of cytotoxicity involved reversal of tributyltin-altered p38 and p44/42 phosphorylation. The results indicated that there was no substantial IL-2 prevention/reversal of the TBT-induced alteration of phosphorylation of either p38 or p44/42 after either a 24 or 48 h recovery period. Additionally, IL-12 caused no substantial prevention/reversal of the TBT-induced alteration of phosphorylation of the MAPKs seen after either 24 or 48 h. These data suggest that IL-2 and/or IL-12-mediated recovery of NK cytotoxic function is not a result of prevention/reversal of TBT-induced phosphorylation of p38 and p44/42 MAPKs at the 24 or 48 h time points. Copyright 2005 John Wiley & Sons, Ltd.

Molecular characterization of thymidine kinase mutants of human cells induced by densely ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Kronenberg, A; Little, J B

1989-04-01

In order to characterize the nature of mutants induced by densely ionizing radiations at an autosomal locus, the authors have isolated a series of 99 thymidine kinase (tk) mutants of human TK6 lymphoblastoid cells iraadiated with either fast neutrons or accelerated argon ions. Individual muant clones were examined for alterations in their restriction fragment pattern after hybridization with a human cDNA probe for tk. A restriction fragment length polymorphism (RFLP) allowed identification of the active tk allele. Among the neutron-induced mutants, 34/52 exhibited loss of the previously active allele while 6/52 exhibited intragenic rearrangements. Among the argon-induced mutants 27/46 exhibited allele loses and 10/46 showed rearrangements within the tk locus. The remaining mutants had restriction patterns indistinguishable from the TK6 parent. Each of the mutant clones was further examined for structural alterations within the c-erbAl locus which has been localized to chromosome 17q11-q22, at some unknown distance from the human tk locus at chromosome 17q21-q22. A substantial proportion (54%) of tk mutants induced by densely ionizing radiation showed loss of the c-erb locus on the homologous chromosome, suggesting that the mutations involve large-scale genetic changes. (author). 51 refs.; 2 figs.; 6 tabs.

Dielectrophoretic deformation of thin liquid films induced by surface charge patterns on dielectric substrates

NARCIS (Netherlands)

Berendsen, C.W.J.; Kuijpers, C.J.; Zeegers, J.C.H.; Darhuber, A.A.

2013-01-01

We studied the deformation of thin liquid films induced by surface charge patterns at the solid–liquid interface quantitatively by experiments and numerical simulations. We deposited a surface charge distribution on dielectric substrates by applying potential differences between a conductive liquid

Altered sleep-wake patterns in blindness

DEFF Research Database (Denmark)

Aubin, S.; Gacon, C.; Jennum, P.

2016-01-01

discuss variability in the sleep–wake pattern between blind and normal-sighted individuals. Methods Thirty-day actigraphy recordings were collected from 11 blind individuals without residual light perception and 11 age- and sex-matched normal-sighted controls. From these recordings, we extracted...... the Pittsburgh Sleep Quality Index, and chronotype, using the Morningness-Eveningness Questionnaire. Results Although no group differences were found when averaging over the entire recording period, we found a greater variability throughout the 30-days in both sleep efficiency and timing of the night-time sleep...

Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

Directory of Open Access Journals (Sweden)

Lara Bull-Otterson

Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme

International Nuclear Information System (INIS)

Shields, Lisa BE; Kadner, Robert; Vitaz, Todd W; Spalding, Aaron C

2013-01-01

We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m 2 ) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m 2 × 5 days) and BEV were delivered monthly until progression or 12 months total. With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ

Arsenic induced clinico-hemato-pathological alterations in broilers and its attenuation by vitamin e and selenium

International Nuclear Information System (INIS)

Mashkoor, J.; Khan, A.; Khan, M.Z.; Saleemi, M.K.; Mahmood, F.

2012-01-01

Present study was carried out to know the arsenic (As) induced toxico-pathological alterations in broiler chicks and their attenuation with vitamin E (Vit E) and selenium (Se). A total of 90 day-old broiler chicks were equally distributed into 5 groups. Groups 1-4 were administered As at 50 mg/kg BW daily through feed for 30 days. In addition to A , groups 2 to 4 received Vitamin E at 150 mg/kg BW, selenium at 0.25 mg/kg BW and Vitamin E plus selenium, respectively. Group 5 (Control) received normal drinking water for 30 days. Dullness, depression, open mouth breathing, increased thirst; ruffled feathers, pale comb, skin irritation and watery diarrhea were the most striking clinical signs. The body weight and feed intake was significantly decreased in treated birds. The erythrocyte counts, hemoglobin concentration and packed cell volume decreased (P<0.05) in treated broilers with As or As with Se and Vit E. Grossly pale and hemorrhagic liver and swollen kidneys were observed in As treated birds. Arsenic treated groups showed significant decrease in serum. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation. In kidneys, condensation of tubular epithelium nuclei, epithelial cell necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed. In conclusion As induced toxico-pathological alterations and vitamin E and selenium partially ameliorate the toxic effects in broilers chicks. (author)

Anisotropic photoconductivity and current deflection induced in Bi12SiO20 by high contrast interference pattern

DEFF Research Database (Denmark)

Kukhtarev, N.V.; Lyuksyutov, S; Buchhave, Preben

1996-01-01

We have predicted and observed an anisotropic photocurrent induced in the cubic crystal Bi/sub 12/SiO/sub 20/ by a high-contrast interference pattern. The transverse current detected when the interference pattern is tilted is caused by deflection of the direct current generated by an external...

Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria

Energy Technology Data Exchange (ETDEWEB)

Tseng, Michael T., E-mail: mttsen01@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Lu, Xiaoqin, E-mail: x0lu0003@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Duan, Xiaoxian, E-mail: x0duan02@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Hardas, Sarita S., E-mail: sarita.hardas@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Sultana, Rukhsana, E-mail: rsult2@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Wu, Peng, E-mail: peng.wu@uky.edu [Dept of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky (United States); Unrine, Jason M., E-mail: jason.unrine@uky.edu [Dept of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky (United States); Graham, Uschi, E-mail: graham@caer.uky.edu [Center for Applied Energy Research, University of Kentucky, Lexington, Kentucky (United States); Butterfield, D. Allan, E-mail: dabcns@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Grulke, Eric A., E-mail: eric.grulke@uky.edu [Dept of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky (United States); Yokel, Robert A., E-mail: ryokel@email.uky.edu [Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (United States)

2012-04-15

Beyond the traditional use of ceria as an abrasive, the scope of nanoceria applications now extends into fuel cell manufacturing, diesel fuel additives, and for therapeutic intervention as a putative antioxidant. However, the biological effects of nanoceria exposure have yet to be fully defined, which gave us the impetus to examine its systemic biodistribution and biological responses. An extensively characterized nanoceria (5 nm) dispersion was vascularly infused into rats, which were terminated 1 h, 20 h or 30 days later. Light and electron microscopic tissue characterization was conducted and hepatic oxidative stress parameters determined. We observed acute ceria nanoparticle sequestration by Kupffer cells with subsequent bioretention in parenchymal cells as well. The internalized ceria nanoparticles appeared as spherical agglomerates of varying dimension without specific organelle penetration. In hepatocytes, the agglomerated nanoceria frequently localized to the plasma membrane facing bile canaliculi. Hepatic stellate cells also sequestered nanoceria. Within the sinusoids, sustained nanoceria bioretention was associated with granuloma formations comprised of Kupffer cells and intermingling CD3{sup +} T cells. A statistically significant elevation of serum aspartate aminotransferase (AST) level was seen at 1 and 20 h, but subsided by 30 days after ceria administration. Further, elevated apoptosis was observed on day 30. These findings, together with increased hepatic protein carbonyl levels on day 30, indicate ceria-induced hepatic injury and oxidative stress, respectively. Such observations suggest a single vascular infusion of nanoceria can lead to persistent hepatic retention of particles with possible implications for occupational and therapeutic exposures. -- Highlights: ► Time course study on nanoceria induced hepatic alterations in rats. ► Serum AST elevation indicated acute hepatotoxicity. ► Ceria is retained for up to 30 days in Kupffer cells

Nanosecond pulsed laser induced self-organized nano-dots patterns on GaSb surface

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Yutaka, E-mail: yyoshida@cris.hokudai.ac.jp [Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan); Creative Research Institution Sousei, Hokkaido University, N21, W10, Kita-ku, Sapporo 001-0021, Hokkaido (Japan); Oosawa, Kazuya; Wajima, Jyunya; Watanabe, Seiichi [Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan); Matsuo, Yasutaka [Research Institute for Electronic Science, Hokkaido University, Sapporo 001-0020, Hokkaido (Japan); Kato, Takahiko [Hitachi Research Laboratory, Hitachi, Ltd., 7-1-1 Omika, Hitachi-shi 319-1292, Ibaraki-ken (Japan); Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan)

2014-07-01

We report a technique for formation of two-dimensional (2D) nanodot (ND) patterns on gaillium antimoide (GaSb) using a nanosecond pulsed laser irradiation with 532 nm wavelength. The patterns have formed because of the interference and the self-organization under energy deposition of the laser irradiation, which induced the growth of NDs on the local area. The NDs are grown and shrunken in the pattern by energy depositions. In the laser irradiation with average laser energy density of 35 mJ cm⁻², large and small NDs are formed on GaSb surface. The large NDs have grown average diameter from 160 to 200 nm with increase of laser pulses, and the small NDs have shrunken average diameter from 75 to 30 nm. The critical dot size is required about 107 nm for growth of the NDs in the patterns. Nanosecond pulsed laser irradiation can control the self-organized ND size on GaSb in air as a function of the laser pulses.

Altered insulin response to an acute bout of exercise in pediatric obesity.

Science.gov (United States)

Tran, Brian D; Leu, Szu-Yun; Oliver, Stacy; Graf, Scott; Vigil, Diana; Galassetti, Pietro

2014-11-01

Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations.

Neuromorphological and wiring pattern alterations effects on brain function: a mixed experimental and computational approach.

Directory of Open Access Journals (Sweden)

Linus Manubens-Gil

2015-04-01

In addition, the study of fixed intact brains (by means of the state of the art CLARITY technique brings us closer to biologically and medically relevant situations, allowing not only to confirm whether the functional links in neuronal cultures are also present in vivo, but also enabling the introduction of functional information (like behavioral studies and functional imaging and another layer of structural alterations such as brain region morphology, neuronal density, and long-range connectivity. Taking together the experimental information from these systems we want to feed self-developed computational models that allow us to understand what are the fundamental characteristics of the observed connectivity patterns and the impact of each of the alterations on neuronal network function. These models will also provide a framework able to account for the emergent properties that bridge the gap between spontaneous electrical activity arousal/transmission and higher order information processing and memory storage capacities in the brain. As an additional part of the project we are now working on the application of the clearing, labeling and imaging protocols to human biopsy samples. Our aim is to obtain neuronal architecture and connectivity information from focal cortical dysplasia microcircuits using samples from intractable temporal lobe epilepsy patients that undergo deep-brain electrode recording diagnosis and posterior surgical extraction of the tissue. Our computational models can allow us to discern the contributions of the observed abnormalities to neuronal hyperactivity and epileptic seizure generation.

New insights into uremia-induced alterations in metabolic pathways.

Science.gov (United States)

Rhee, Eugene P; Thadhani, Ravi

2011-11-01

This article summarizes recent studies on uremia-induced alterations in metabolism, with particular emphasis on the application of emerging metabolomics technologies. The plasma metabolome is estimated to include more than 4000 distinct metabolites. Because these metabolites can vary dramatically in size and polarity and are distributed across several orders of magnitude in relative abundance, no single analytical method is capable of comprehensive metabolomic profiling. Instead, a variety of analytical techniques, including targeted and nontargeted liquid chromatography-mass spectrometry, have been employed for metabolomic analysis of human plasma. Recent efforts to apply this technology to study uremia have reinforced the common view that end-stage renal disease is a state of generalized small molecule excess. However, the identification of precursor depletion and downstream metabolite excess - for example, with tryptophan and downstream kynurenine metabolites, with low molecular weight triglycerides and dicarboxylic acids, and with phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia may directly modulate these metabolic pathways. Metabolomic studies have also begun to expand some of these findings to individuals with chronic kidney disease and in model systems. Uremia is associated with diverse, but incompletely understood metabolic disturbances. Metabolomic approaches permit higher resolution phenotyping of these disturbances, but significant efforts will be required to understand the functional significance of select findings.

Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells

Directory of Open Access Journals (Sweden)

Cynthia C.T. Sprenger

2008-12-01

Full Text Available Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer.

Haemato-biochemical alterations induced by lead acetate toxicity in wistar rats

Directory of Open Access Journals (Sweden)

S. G. Suradkar

Full Text Available An experiment was conducted to study the haemato-biochemical alterations induced by lead acetate toxicity in 48 Wistar rats of either sex, divided uniformly into four different groups. The rats of group I received only deionised water as control while, group II, III and IV were given lead acetate @ 1 PPM, 100 PPM and 1000 PPM, in drinking deionised water respectively for 28 days. In group III and IV dose dependant significant (P<0.05 reductions in TEC, Hb, PCV and TLC were observed. No significant change was observed in neutrophil, eosinophil, basophil and monocyte count in any treatment groups, whereas the lymphocyte count decreased significantly (P<0.05 in group III and IV. A dose dependant significant (P<0.05 increase in AST, ALP, AKP, GGT, BUN and creatinine was experiential while TP and albumin levels were decreased in group III and IV. [Vet World 2009; 2(11.000: 429-431

Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

Science.gov (United States)

Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

2014-02-01

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice.

Science.gov (United States)

Ben Salah-Abbès, Jalila; Abbès, Samir; Abdel-Wahhab, Mosaad A; Oueslati, Ridha

2009-04-01

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.

Altered doppler flow patterns in cirrhosis patients: An overview

Energy Technology Data Exchange (ETDEWEB)

Iranpour, Pooya; Lall, Chandana; Houshyar, Roozbeh; Helmy, Mohammad; Yang, Albert; Ward, Garrett; Goodwin, Scott C. [Dept. of Radiology, University of California Irvine, Orange (United States); Choi, Joon Il [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2016-01-15

Doppler ultrasonography of the hepatic vasculature is an integral part of evaluating precirrhotic and cirrhotic patients. While the reversal of the portal venous flow is a well-recognized phenomenon, other flow patterns, although not as easily understood, may play an important role in assessing the disease status. This article discusses the different characteristic flow patterns observed from the portal vein, hepatic artery, and hepatic vein in patients with liver cirrhosis or related complications and procedures. Knowledge of these different flow patterns provides additional information that may reinforce the diagnosis of cirrhosis, help in staging, and offer prognostic information for determining the direction of therapy. Doppler ultrasonography is invaluable when liver transplantation is being considered and aids in the diagnosis of cirrhosis and portal hypertension.

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

Science.gov (United States)

Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

2016-01-01

Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

Science.gov (United States)

Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

2010-12-01

Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

Directory of Open Access Journals (Sweden)

Thiago Bruder-Nascimento

2015-06-01

Full Text Available Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load, stressed (2 h-immobilization, and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10. Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary. Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed. Indomethacin determined a decrease in sensitivity (EC50 in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination.

Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

Directory of Open Access Journals (Sweden)

William P Lafuse

Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

Science.gov (United States)

Afzal, Muhammad; Kazmi, Imran; Khan, Ruqaiyah; Rana, Poonam; Kumar, Vikas; Al-Abbasi, Fahad A; Zamzami, Mazin A; Anwar, Firoz

2017-06-01

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

Energy Technology Data Exchange (ETDEWEB)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States)

2012-05-15

Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

Directory of Open Access Journals (Sweden)

RN Jadeja

Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

Characterization of 6,13-bis(triisopropylsilylethynyl) pentacene organic thin film transistors fabricated using pattern-induced confined structure

International Nuclear Information System (INIS)

Kim, Kyohyeok; Kwon, Namyong; Chung, Ilsub

2014-01-01

Bottom gate organic thin film transistors (OTFTs) were fabricated on polyethersulphone substrate using an ink jet printing method. 6,13-bis(triisopropylsilylethynyl) (TIPS) pentacene and poly-4-vinylphenol (PVP) were used as an active material and as a gate insulator, respectively. In an attempt to reduce the coffee stain effect, TIPS pentacene active layer was printed onto the pattern-induced confined structure (PICS) which had been obtained by orthogonally printing Ag electrodes on the pre-printed PVP layer. The resolution of Ag patterns was obtained by modifying the surface energy using UV irradiation and substrate temperature. The channel lengths of the aforementioned PICS OTFTs were in the range of 10 μm to 50 μm. The average mobility and on/off ratio of PICS OTFTs were 0.034 cm 2 /Vs and 10 3 , respectively. - Highlights: • Ink-jet printed bottom gate organic thin film transistor on plastic substrate • Ag lines orthogonally printed on pre-printed poly-4-vinylphenol lines • Pattern-induced confined structures obtained • UV irradiation affects the surface energy and the resolution of the Ag patterns

High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

Science.gov (United States)

Meyers, Allison M; Mourra, Devry; Beeler, Jeff A

2017-01-01

The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

Directory of Open Access Journals (Sweden)

Allison M Meyers

Full Text Available The contribution of high fructose corn syrup (HFCS to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6 received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats

International Nuclear Information System (INIS)

Pari, Leelavinothan; Murugavel, Ponnusamy

2007-01-01

Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3 mg/kg/day subcutaneously) for 3 weeks, a significant (P + K + -ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase) were observed in brain tissue. Oral administration of DTS (40 mg/kg/day) with Cd significantly (P < 0.05) diminished the levels of LPO and protein carbonyls and significantly (P < 0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd

Overexpression of Human-Derived DNMT3A Induced Intergenerational Inheritance of Active DNA Methylation Changes in Rat Sperm

Directory of Open Access Journals (Sweden)

Xiaoguo Zheng

2017-12-01

Full Text Available DNA methylation is the major focus of studies on paternal epigenetic inheritance in mammals, but most previous studies about inheritable DNA methylation changes are passively induced by environmental factors. However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable. Here, we established human-derived DNMT3A (hDNMT3A transgenic rats to study the effect of hDNMT3A overexpression on the DNA methylation pattern of rat sperm and to investigate whether this actively altered DNA methylation status is inheritable. Our results revealed that hDNMT3A was overexpressed in the testis of transgenic rats and induced genome-wide alterations in the DNA methylation pattern of rat sperm. Among 5438 reliable loci identified with 64 primer-pair combinations using a methylation-sensitive amplification polymorphism method, 28.01% showed altered amplified band types. Among these amplicons altered loci, 68.42% showed an altered DNA methylation status in the offspring of transgenic rats compared with wild-type rats. Further analysis based on loci which had identical DNA methylation status in all three biological replicates revealed that overexpression of hDNMT3A in paternal testis induced hypermethylation in sperm of both genotype-negative and genotype-positive offspring. Among the differentially methylated loci, 34.26% occurred in both positive and negative offspring of transgenic rats, indicating intergenerational inheritance of active DNA methylation changes in the absence of hDNM3A transmission. Furthermore, 75.07% of the inheritable loci were hyper-methylated while the remaining were hypomethylated. Distribution analysis revealed that the DNA methylation variations mainly occurred in introns and intergenic regions. Functional analysis revealed that genes related to differentially methylated loci were involved in a wide range of functions. Finally, this study demonstrated that active DNA methylation

Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

Directory of Open Access Journals (Sweden)

Hicks Steven D

2012-10-01

Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

Science.gov (United States)

Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

2013-01-01

A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity

Directory of Open Access Journals (Sweden)

Pauza Mary E

2008-03-01

Full Text Available Abstract A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN. The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ-induced and transgene-mediated murine models of type 1 diabetes (T1D, we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1 expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated T1D are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPV1 as determined by paw withdrawal latency (PWL. An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPV1-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX binding, a measure of TRPV1 expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion (DRG, and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPV1 expression, respectively. A role for TRPV1 in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPV1 deficient mice. These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception.

Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

Science.gov (United States)

Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

2014-01-01

Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene.

Science.gov (United States)

Daghestani, Maha H; Selim, Manar E; Abd-Elhakim, Yasmina M; Said, Enas N; El-Hameed, Noura E Abd; Khalil, Samah R; El-Tawil, Osama S

2017-09-01

The efficacy of apitoxin (bee venom; BV) in ameliorating propionic acid (PPA) -induced neurobehavioral impacts was studied. Sixty rat pups were enrolled in a split litter design to six groups: a control group, a PPA-treated group, a BV-treated group, a BV/PPA protective group, a PPA/BV therapeutic group, and a BV/PPA/BV protective and therapeutic group. Exploratory, social, locomotor, and repetitive/stereotype-like activities were assessed and prosocial, empathy, and acquired behavior were evaluated. Levels of neurotransmitter including serotonin, dopamine, and gamma-aminobutyric acid (GABA) were determined and a quantitative analysis of Reelin gene expression was performed. PPA treatment induced several behavioral alterations, as reduced exploratory activity and social behaviors, increased repetitive/stereotypic behaviors, and hyperactivity. In addition, a marked decline of neurotransmitters and down-regulation of Reelin mRNA expression were observed. BV exhibited high efficiency in ameliorating the PPA-induced neurobehavioral alterations, particularly when applied both before and after PPA administration. Overall, the results implied that BV has merit as a candidate therapeutic treatment to alleviate PPA-induced neurobehavioral disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

Science.gov (United States)

Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

2017-06-01

Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (Pjuice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

2002-11-01

We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons.

Science.gov (United States)

Sabbar, M; Delaville, C; De Deurwaerdère, P; Benazzouz, A; Lakhdar-Ghazal, N

2012-05-17

Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. Male Sprague-Dawley rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d i.p.) during 3 weeks. The tissue content of monoamines was used to determine alteration of these systems at the end of experiments. Results show that lead significantly reduced exploratory activity, locomotor activity and the time spent on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like" behavior. The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Does circumcision alter the periurethral uropathogenic bacterial flora

African Journals Online (AJOL)

Background: The aim of this study was to assess the pattern of periurethral bacterial flora in uncircumcised boys and to evaluate the effect of circumcision on alteration of periurethral uropathogenic bacterial flora. Materials and Methods: Pattern of periurethral bacterial flora before and after circumcision was studied ...

Histological and histochemical alterations in the kidney induced by lead

International Nuclear Information System (INIS)

Jarrar, Bashir M.

2003-01-01

Although lead intoxication is one of the most common forms of metal intoxication,the histochemichal alterations in renal tissues due to chronic lead exposure is limited and has not yet been well identified. A total of 60 male Wistar albino rats were exposed to lead acetate trihydrate( 0.0, 0.25, 0.5, 1.0 and 2% for 1 to 12 months) in drinking water to investigate the histological and histochemical alterations in renal tissues due to lead. Chronic exposure to the subtoxic doses of lead produced distinct progressive tubular, glomerular and interstitial damages. Tubular changes occured earlier than the glomerular and interstitial ones,and included anisokaryosis, nuclear pyknosis,karyomeglay, development of intranuclear cytoplasmic inclusions together with tubular dilation, necrosis,vacuolization, tubular hyperplasia and solid tubular adenoma. The glomrular alterations were mainly mesangial hypercellularity, segmental glomerulosclerosis, glomerular hyalinization and glomerular tuft alterations. The findings indicate that lead produces significant histological and histochemical changes in the kidney that lead to severe complications. (author)

Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

Science.gov (United States)

Nocca, G; De Palma, F; Minucci, A; De Sole, P; Martorana, G E; Callà, C; Morlacchi, C; Gozzo, M L; Gambarini, G; Chimenti, C; Giardina, B; Lupi, A

2007-03-01

Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Alterations in the nuclear matrix protein mass correlate with heat-induced inhibition of DNA single-strand-break repair

International Nuclear Information System (INIS)

Warters, R.L.; Brizgys, L.M.; Lyons, B.W.

1987-01-01

The total protein mass co-isolating with the nuclear matrix or nucleoid from Chinese hamster ovary (CHO) cells was observed to increase in heated cells as a function of increasing exposure temperature between 43 0 C and 45 0 C or of exposure time at any temperature. The sedimentation distance of the CHO cell nucleoid in sucrose gradients increased with increasing exposure time at 45 0 C. Both these nuclear alterations correlated in a log-linear manner with heat-induced inhibition of DNA strand break repair. A two-fold threshold increase in nuclear matrix protein mass preceded any substantial inhibition of repair of DNA single-strand breaks. When preheated cells were incubated at 37 0 C the nuclear matrix protein mass and nucleoid sedimentation recovered with a half-time of about 5 h, while DNA single-strand-break repair recovered with a half-time of about 2 h. When preheated cells were placed at 41 0 C a further increase was observed in the nuclear matrix protein mass and the half-time of DNA strand break repair, while nucleoid sedimentation recovered toward control values. These results implicate alterations in the protein mass of the nuclear matrix in heat-induced inhibition of repair of DNA single-strand breaks. (author)

Formation of precise 2D Au particle arrays via thermally induced dewetting on pre-patterned substrates

Directory of Open Access Journals (Sweden)

Dong Wang

2011-06-01

Full Text Available The fabrication of precise 2D Au nanoparticle arrays over a large area is presented. The technique was based on pre-patterning of the substrate before the deposition of a thin Au film, and the creation of periodic particle arrays by subsequent dewetting induced by annealing. Two types of pre-patterned substrates were used: The first comprised an array of pyramidal pits and the second an array of circular holes. For the dewetting of Au films on the pyramidal pit substrate, the structural curvature-driven diffusion cooperates with capillarity-driven diffusion, resulting in the formation of precise 2D particle arrays for films within a structure dependent thickness-window. For the dewetting of Au films on the circular hole substrate, the periodic discontinuities in the films, induced by the deposition, can limit the diffusion paths and lead to the formation of one particle per individual separated region (holes or mesas between holes, and thus, result in the evolution of precise 2D particle arrays. The influence of the pre-patterned structures and the film thickness is analyzed and discussed. For both types of pre-patterned substrate, the Au film thickness had to be adjusted in a certain thickness-window in order to achieve the precise 2D particle arrays.

Formation of precise 2D Au particle arrays via thermally induced dewetting on pre-patterned substrates

Science.gov (United States)

Ji, Ran

2011-01-01

Summary The fabrication of precise 2D Au nanoparticle arrays over a large area is presented. The technique was based on pre-patterning of the substrate before the deposition of a thin Au film, and the creation of periodic particle arrays by subsequent dewetting induced by annealing. Two types of pre-patterned substrates were used: The first comprised an array of pyramidal pits and the second an array of circular holes. For the dewetting of Au films on the pyramidal pit substrate, the structural curvature-driven diffusion cooperates with capillarity-driven diffusion, resulting in the formation of precise 2D particle arrays for films within a structure dependent thickness-window. For the dewetting of Au films on the circular hole substrate, the periodic discontinuities in the films, induced by the deposition, can limit the diffusion paths and lead to the formation of one particle per individual separated region (holes or mesas between holes), and thus, result in the evolution of precise 2D particle arrays. The influence of the pre-patterned structures and the film thickness is analyzed and discussed. For both types of pre-patterned substrate, the Au film thickness had to be adjusted in a certain thickness-window in order to achieve the precise 2D particle arrays. PMID:21977445

Molecular alterations underlying the spontaneous and γ-ray-induced point mutations at the white locus of Drosophila Melanogaster

International Nuclear Information System (INIS)

Aleksandrova, M.V.; Lapidus, I.L.; Aleksandrov, I.D.; Karpovskij, A.L.

1996-01-01

The white locus in D.Melanogaster was selected as a target gene for the study of the mutational spectra of spontaneously arising and radiation-induced gene mutations in a whole organism. Analysis of 6 spontaneous and 73 γ-ray-induced white mutations by a combination of cytological, genetic and molecular techniques revealed that on the chromosomal and genetic levels all spontaneous mutations showed themselves to be point mutants. The share of such mutants among all heritable radiation-induced gene mutations is about 40%, whereas the rest ones are due to exchange breaks (8%) as well as multilocus, single-locus or partial-locus (intragenic) deletions (52%). The DNAs from 4 spontaneous and 17 γ-ray-induced point mutants were analysed by Southern blot-hybridization. The three spontaneous and 7 radiation mutants showed an altered DNA sequence at the left (distal) half of the white gene due to insertion or DNA rearrangement. The rest (58%) of the radiation-induced point mutations did not indicate any alternations in this part of the gene as detected by this technique and probes employed. 15 refs., 3 figs., 1 tab

Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system.

Science.gov (United States)

Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

2015-12-21

We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.

Science.gov (United States)

Lee, David E; Brown, Jacob L; Rosa-Caldwell, Megan E; Blackwell, Thomas A; Perry, Richard A; Brown, Lemuel A; Khatri, Bhuwan; Seo, Dongwon; Bottje, Walter G; Washington, Tyrone A; Wiggs, Michael P; Kong, Byung-Whi; Greene, Nicholas P

2017-05-01

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia. Copyright © 2017 the American Physiological Society.

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

Science.gov (United States)

Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

2016-09-01

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its

Colchicine affects cell motility, pattern formation and stalk cell differentiation in Dictyostelium by altering calcium signaling.

Science.gov (United States)

Poloz, Yekaterina; O'Day, Danton H

2012-04-01

Previous work, verified here, showed that colchicine affects Dictyostelium pattern formation, disrupts morphogenesis, inhibits spore differentiation and induces terminal stalk cell differentiation. Here we show that colchicine specifically induces ecmB expression and enhances accumulation of ecmB-expressing cells at the posterior end of multicellular structures. Colchicine did not induce a nuclear translocation of DimB, a DIF-1 responsive transcription factor in vitro. It also induced terminal stalk cell differentiation in a mutant strain that does not produce DIF-1 (dmtA-) and after the treatment of cells with DIF-1 synthesis inhibitor cerulenin (100 μM). This suggests that colchicine induces the differentiation of ecmB-expressing cells independent of DIF-1 production and likely through a signaling pathway that is distinct from the one that is utilized by DIF-1. Depending on concentration, colchicine enhanced random cell motility, but not chemotaxis, by 3-5 fold (10-50 mM colchicine, respectively) through a Ca(2+)-mediated signaling pathway involving phospholipase C, calmodulin and heterotrimeric G proteins. Colchicine's effects were not due to microtubule depolymerization as other microtubule-depolymerizing agents did not have these effects. Finally normal morphogenesis and stalk and spore cell differentiation of cells treated with 10 mM colchicine were rescued through chelation of Ca2+ by BAPTA-AM and EDTA and calmodulin antagonism by W-7 but not PLC inhibition by U-73122. Morphogenesis or spore cell differentiation of cells treated with 50 mM colchicine could not be rescued by the above treatments but terminal stalk cell differentiation was inhibited by BAPTA-AM, EDTA and W-7, but not U-73122. Thus colchicine disrupts morphogenesis and induces stalk cell differentiation through a Ca(2+)-mediated signaling pathway involving specific changes in gene expression and cell motility. Copyright © 2011 International Society of Differentiation. Published by Elsevier B

Protective role of Tinospora cordifolia extract against radiation-induced qualitative, quantitative and biochemical alterations in testes

International Nuclear Information System (INIS)

Sharma, Priyanka; Parmar, Jyoti; Sharma, Priyanka; Verma, Preeti; Goyal, P.K.

2012-01-01

In today's changing global scenario, ionizing radiation is considered as most potent cause of oxidative stress mediated by free radical flux which induces severe damage at various hierarchical levels in the organization in the living organisms. Testis is a highly prolific tissue with fast cellular renewal and poor antioxidant defense; therefore it becomes an easy target for the radiation-induced free radicals that have long been suggested as major cause of male infertility. Chemical radioprotection is an important strategy to countermeasure the deleterious effects of radiation. Several Indian medicinal plants are rich source of antioxidants and these have been used for the treatment of ailments. Tinospora cordifolia, commonly known as amrita, is one of the plants that have several pharmacological and therapeutic properties. Therefore, the present study was performed to evaluate the deleterious effects of semi lethal dose of gamma radiation on testicular tissue and their possible inhibition by Tinospora cordifolia root extract (TCE). For this purpose, healthy Swiss albino male mice were selected from an inbred colony and divided into four groups. Group I (normal) was administered double distilled water (DDW) volume equal to TCE (75 mg/kg.b.wt/animal) by oral gavage. Group II was orally supplemented TCE as 75 mg/kg. b.wt once daily for 5 consecutive days. Group III (irradiated control) received DDW orally equivalent to TCE for 5 days then exposed to 5 Gy gamma radiation. Group IV (experimental) was administered TCE as in Group II and exposed to radiation (as in Group III). Irradiation resulted into significant decrease in the frequency of different spermatogenic cell counts along with severe histo-pathological lesions up to 7th day of irradiation in testes of irradiated control animals, thereafter, recovery followed towards the normal architecture. TCE pretreatment effectively prevented radiation induced such alterations in cellular counts and testicular injuries by

Alterations and abnormal mitosis of wheat chromosomes induced by wheat-rye monosomic addition lines.

Directory of Open Access Journals (Sweden)

Shulan Fu

Full Text Available BACKGROUND: Wheat-rye addition lines are an old topic. However, the alterations and abnormal mitotic behaviours of wheat chromosomes caused by wheat-rye monosomic addition lines are seldom reported. METHODOLOGY/PRINCIPAL FINDINGS: Octoploid triticale was derived from common wheat T. aestivum L. 'Mianyang11'×rye S. cereale L. 'Kustro' and some progeny were obtained by the controlled backcrossing of triticale with 'Mianyang11' followed by self-fertilization. Genomic in situ hybridization (GISH using rye genomic DNA and fluorescence in situ hybridization (FISH using repetitive sequences pAs1 and pSc119.2 as probes were used to analyze the mitotic chromosomes of these progeny. Strong pSc119.2 FISH signals could be observed at the telomeric regions of 3DS arms in 'Mianyang11'. However, the pSc119.2 FISH signals were disappeared from the selfed progeny of 4R monosomic addition line and the changed 3D chromosomes could be transmitted to next generation stably. In one of the selfed progeny of 7R monosomic addition line, one 2D chromosome was broken and three 4A chromosomes were observed. In the selfed progeny of 6R monosomic addition line, structural variation and abnormal mitotic behaviour of 3D chromosome were detected. Additionally, 1A and 4B chromosomes were eliminated from some of the progeny of 6R monosomic addition line. CONCLUSIONS/SIGNIFICANCE: These results indicated that single rye chromosome added to wheat might cause alterations and abnormal mitotic behaviours of wheat chromosomes and it is possible that the stress caused by single alien chromosome might be one of the factors that induced karyotype alteration of wheat.

Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

Science.gov (United States)

Areal, Lorena Bianchine; Herlinger, Alice Laschuk; Pelição, Fabrício Souza; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

2017-08-01

Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pattern Of Altered Lipid Profile In Patients With Subclinical And Clinical Hypothyroidism And Its Correlation With Body Mass Index

International Nuclear Information System (INIS)

Humerah, S.; Siddiqui, A.; Khan, H. F.

2016-01-01

Objective: To compare the lipid profile of the subclinical and clinical hypothyroid patients and to evaluate the correlation between body mass index (BMI) and lipid profile in hypothyroidism. Study Design: Cross-sectional study. Place and Duration of Study: Islamic International Medical College, Riphah International University, Islamabad, and Citi Laboratory, Rawalpindi, from January to December 2013. Methodology: The subjects were selected through non-probability, purposive sampling. On the basis of thyroid profile, the subjects were divided into 3 groups: euthyroids (n=20), subclinical hypothyroids (n=50), and clinical hypothyroids (n=30). The blood of these subjects was then analyzed for lipid profile. Data was analyzed using SPSS version 18 statistical software. Result: Both hypothyroid groups showed altered lipid profile which was observed to be significantly raised when compared with the euthyroid subjects. Comparison of lipid profile in euthyroid, subclinical, and clinical hypothyroid groups showed significant differences by non-parametric tests (p < 0.05). An assessment of correlation of lipid profile with the BMI was found to be significant (p < 0.01). Conclusion: Hypothyroidism causes alteration of lipid profile. Clinical and subclinical hypothyroid patients have altered lipid profile as compared to euthyroids. Thyroid status monitoring is very important, since it can induce changes in lipid profile. Such dyslipidemic status is significant not only for the management of thyroid disorders but also for common diseases like obesity and coronary atherosclerosis in the population. (author)

Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells1

Science.gov (United States)

Sprenger, Cynthia C T; Drivdahl, Rolf H; Woodke, Lillie B; Eyman, Daniel; Reed, May J; Carter, William G; Plymate, Stephen R

2008-01-01

Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs) are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer. PMID:19048114

Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

Science.gov (United States)

Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

2012-08-30

Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

2018-04-01

Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

Characterization of 6,13-bis(triisopropylsilylethynyl) pentacene organic thin film transistors fabricated using pattern-induced confined structure

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyohyeok; Kwon, Namyong [Sungkyunkwan University Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Chung, Ilsub, E-mail: ichung@skku.ac.kr [Sungkyunkwan University Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); College of Information and Communication Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2014-01-01

Bottom gate organic thin film transistors (OTFTs) were fabricated on polyethersulphone substrate using an ink jet printing method. 6,13-bis(triisopropylsilylethynyl) (TIPS) pentacene and poly-4-vinylphenol (PVP) were used as an active material and as a gate insulator, respectively. In an attempt to reduce the coffee stain effect, TIPS pentacene active layer was printed onto the pattern-induced confined structure (PICS) which had been obtained by orthogonally printing Ag electrodes on the pre-printed PVP layer. The resolution of Ag patterns was obtained by modifying the surface energy using UV irradiation and substrate temperature. The channel lengths of the aforementioned PICS OTFTs were in the range of 10 μm to 50 μm. The average mobility and on/off ratio of PICS OTFTs were 0.034 cm{sup 2}/Vs and 10{sup 3}, respectively. - Highlights: • Ink-jet printed bottom gate organic thin film transistor on plastic substrate • Ag lines orthogonally printed on pre-printed poly-4-vinylphenol lines • Pattern-induced confined structures obtained • UV irradiation affects the surface energy and the resolution of the Ag patterns.

Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis

Energy Technology Data Exchange (ETDEWEB)

Abdelali, Ala [Department of Anatomy, Faculty of Medicine, Kuwait University (Kuwait); Al-Bader, Maie [Department of Physiology, Faculty of Medicine, Kuwait University (Kuwait); Kilarkaje, Narayana, E-mail: knarayana@hsc.edu.kw [Department of Anatomy, Faculty of Medicine, Kuwait University (Kuwait)

2016-11-15

Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22–42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis. - Highlights: • Resveratrol inhibits diabetes-induced abnormal sperm morphogenesis • Resveratrol recovers

Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis

International Nuclear Information System (INIS)

Abdelali, Ala; Al-Bader, Maie; Kilarkaje, Narayana

2016-01-01

Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22–42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis. - Highlights: • Resveratrol inhibits diabetes-induced abnormal sperm morphogenesis • Resveratrol recovers

Treeline proximity alters an alpine plant-herbivore interaction.

Science.gov (United States)

Illerbrun, Kurt; Roland, Jens

2011-05-01

Rising treeline threatens the size and contiguity of alpine meadows worldwide. As trees encroach into previously open habitat, the movement and population dynamics of above-treeline alpine species may be disrupted. This process is well documented in studies of the Rocky Mountain apollo butterfly (Parnassius smintheus). However, subtler consequences of treeline rise remain poorly understood. In this study, we examine whether treeline proximity affects feeding behaviour of P. smintheus larvae, due to altered habitat affecting the distribution and availability of their host plant, lance-leaved stonecrop (Sedum lanceolatum). Understanding differential larval exploitation of food resources in relation to the treeline is an important step in predicting the consequences of continued treeline rise. Parnassius smintheus larvae feed more intensively on S. lanceolatum away from the treeline despite the relative paucity of hosts in these areas, and despite higher fitness penalties associated with the plant's herbivory-induced chemical defenses. Sedum lanceolatum growing near the treeline is less attractive, and therefore represents a less significant resource for P. smintheus larvae than its abundance might imply. If treeline rise continues, we suggest that this pattern of altered resource exploitation may represent a mechanism by which larvae are adversely affected even while adult movement among and within meadows appears sufficient for maintaining population health, and total host availability seems ample.

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

Science.gov (United States)

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Calculation of diffraction patterns associated with electron irradiation induced amorphization of CuTi

International Nuclear Information System (INIS)

Devanathan, R.; Meshii, M.; Sabochik, M.J.

1990-11-01

A new approach that uses the multislice method in conjunction with molecular dynamics simulations to study electron irradiation induced amorphisation is presented. Diffraction patterns were calculated for CuTi and found to be more sensitive than the pair correlation function to the structural changes preceding amorphisation. The results from this approach and from a study of long range order are presented. 16 refs., 8 figs

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

Science.gov (United States)

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oesophageal epithelial cell proliferation and food consumption patterns following irradiation

International Nuclear Information System (INIS)

Burholt, D.R.

1986-01-01

The murine data presented illustrate the influence of food consumption on the proliferative rate of the oesophageal epithelium during recovery from radiation damage. Refeeding at a time before the initiation of the normal hyperplastic response results in a decreased time interval between treatment and increased rates of cell proliferation, while reduced food consumption during the normal period of hyperproliferation results in reduced proliferative activity. The finding that recovery kinetics may be altered by changing food consumption patterns should be an important consideration in the analysis of antineoplastic agent-induced proliferative perturbations, as many treatments themselves produce reduced levels of food consumption. (UK)

Casticin induced apoptotic cell death and altered associated gene expression in human colon cancer colo 205 cells.

Science.gov (United States)

Shang, Hung-Sheng; Liu, Jia-You; Lu, Hsu-Feng; Chiang, Han-Sun; Lin, Chia-Hain; Chen, Ann; Lin, Yuh-Feng; Chung, Jing-Gung

2017-08-01

Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca 2+ productions, level of mitochondria membrane potential (ΔΨ m ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death. Casticin induced cell morphological changes, decreased cell viability and induced G2/M phase arrest in colo 205 cells. Casticin increased ROS production but decreased the levels of ΔΨ m , and Ca 2+ , increased caspase-3, -8, and -9 activities. The cDNA microarray indicated that some of the cell cycle associated genes were down-regulated such as cyclin-dependent kinase inhibitor 1A (CDKN1A) (p21, Cip1) and p21 protein (Cdc42/Rac)-activated kinase 3 (PAK3). TNF receptor-associated protein 1 (TRAP1), CREB1 (cAMP responsive element binding protein 1) and cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27, Kip1) genes were increased but matrix metallopeptidase 2 (MMP-2), toll-like receptor 4 (TLR4), PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, bet), and CaMK4 (calcium/calmodulin-dependent protein kinase IV) genes were inhibited. Results suggest that casticin induced cell apoptosis via the activation of the caspase- and/or mitochondria-dependent signaling cascade, the accumulation of ROS and altered associated gene expressions in colo 205 human colon cancer cells. © 2016 Wiley Periodicals, Inc.

Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus

Directory of Open Access Journals (Sweden)

JOSÉ MIGUEL ROJAS

2005-01-01

Full Text Available A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996, suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts

Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus.

Science.gov (United States)

Rojas, José Miguel; Ojeda, F Patricio

2005-01-01

A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996), suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts.

Gait pattern alteration by functional sensory substitution in healthy subjects and in diabetic subjects with peripheral neuropathy.

Science.gov (United States)

Walker, S C; Helm, P A; Lavery, L A

1997-08-01

To evaluate the ability of diabetic and nondiabetic individuals to learn to use a lower extremity sensory substitution device to cue gait pattern changes. Case-control study. Gait laboratory. Thirty diabetic persons and 20 age- and education-matched nondiabetic controls responded to advertisements for study participation. Participants walked on a treadmill at three speeds (1, 2, and 2.5mph) with auditory sensory feedback to cue ground contact greater than 80% duration of baseline. The variables measured included gait cycle (steps per minute) and number of times per minute that any step during a trial exceeded 80% duration of ground contacted compared with a measured baseline step length for each speed. Persons in both groups were able to rapidly and significantly alter their gait patterns in response to signals from the sensory substitution device, by changing their gait cycles (nondiabetic group, F(17,124) = 5.27, p gait cycle modification and error reduction among both groups. The nondiabetic group learned to use the device significantly more quickly than the diabetic group during the slow (1mph, t = 3.57, p gait trainer malfunction occurred during the study. Diabetic persons with neuropathy effectively used lower extremity sensory substitution, and the technology is now available to manufacture a durable, effective lower extremity sensory substitution system.

Altered Cellular Metabolism Drives Trained Immunity.

Science.gov (United States)

Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

2018-04-04

Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43.

Directory of Open Access Journals (Sweden)

Merlin Nanayakkara

Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP gene was identified as strongly associated with CD using genome-wide association studies (GWAS. The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.

Analysis of time-varying psoriasis lesion image patterns

DEFF Research Database (Denmark)

Maletti, Gabriela Mariel; Ersbøll, Bjarne Kjær; Nielsen, Allan Aasbjerg

2004-01-01

The multivariate alteration detection transform is applied to pairs of within and between time varying registered psoriasis image patterns. Color band contribution to the variates explaining maximal change is analyzed.......The multivariate alteration detection transform is applied to pairs of within and between time varying registered psoriasis image patterns. Color band contribution to the variates explaining maximal change is analyzed....

Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

Science.gov (United States)

Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

Science.gov (United States)

Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Adachi, Lauren Naomi Spezia; de Macedo, Isabel Cristina; Cioato, Stefania Giotti; de Freitas, Joice S; de Souza, Andressa; Quevedo, Alexandre; Caumo, Wolnei; Torres, Iraci Lucena da Silva

2016-10-01

Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

Directory of Open Access Journals (Sweden)

Daina S. E. Dickins

2015-01-01

Full Text Available Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years underwent intermittent theta burst stimulation (iTBS whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

Science.gov (United States)

Dickins, Daina S. E.; Sale, Martin V.

2015-01-01

Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

Acupuncture induces divergent alterations of functional connectivity within conventional frequency bands: evidence from MEG recordings.

Directory of Open Access Journals (Sweden)

Youbo You

Full Text Available As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36 and a nearby non-meridian point (NAP would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz, beta (13-30 Hz and gamma (30-48 Hz bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend

Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.

Science.gov (United States)

Petricoin, Emanuel F; Rajapaske, Vinodh; Herman, Eugene H; Arekani, Ali M; Ross, Sally; Johann, Donald; Knapton, Alan; Zhang, J; Hitt, Ben A; Conrads, Thomas P; Veenstra, Timothy D; Liotta, Lance A; Sistare, Frank D

2004-01-01

Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity.

Offspring reaction norms shaped by parental environment: interaction between within- and trans-generational plasticity of inducible defenses.

Science.gov (United States)

Luquet, Emilien; Tariel, Juliette

2016-10-12

Within-generational plasticity (WGP) and transgenerational plasticity (TGP) are mechanisms allowing rapid adaptive responses to fluctuating environments without genetic change. These forms of plasticity have often been viewed as independent processes. Recent evidence suggests that WGP is altered by the environmental conditions experienced by previous generations (i.e., TGP). In the context of inducible defenses, one of the most studied cases of plasticity, the WGP x TGP interaction has been poorly investigated. We provide evidence that TGP can alter the reaction norms of inducible defenses in a freshwater snail. The WGP x TGP interaction patterns are trait-specific and lead to decreased slope of reaction norms (behaviour and shell thickness). Offspring from induced parents showed a higher predator avoidance behaviour and a thicker shell than snails from non-induced parents in no predator-cue environment while they reached similar defenses in predator-cue environment. The WGP x TGP interaction further lead to a switch from a plastic towards a constitutive expression of defenses for shell dimensions (flat reaction norm). WGP-alteration by TGP may shape the adaptive responses to environmental change and then has a substantial importance to understand the evolution of plasticity.

Exposure and Figure Out of Climate Induced Alterations in the Wetlands of Banglades

Science.gov (United States)

Siddiquee, S. A.; Rahman, M. Z.

2015-12-01

Unique geographic location and geo-morphological conditions of Bangladesh have made the wetlands of this country one of the most vulnerable to climate change. Wetland plays a crucial role in maintaining the ecological balance of ecosystems and cultural figures and which occupy around 50% of the area. Drought, excessive temperature, mountain snowfields and glaciers melting, riverbank erosion, salinity intrusion, flashflood, storm surges, higher water temperatures, precipitation anomalies, coastal cyclones, seasonal anomalies and extremes are main threats to the wetland ecosystem. Enhanced UV-B radiation and increased summer precipitation will significantly increase dissolved organic carbon concentrations altering major biogeochemical cycles and also will result into the expansion of range for many invasive aquatic weeds. Generally, rising temperature will lower water quality through a fall in oxygen concentrations, release of phosphorus from sediments, increased thermal stability, and altered mixing patterns. As a result biodiversity is getting degraded, many species of flora and fauna are getting threatened, and wetland-based ecosystem is getting degenerated. At the same time, the living conditions of local people are deteriorating as livelihoods, socioeconomic institutions, and extensive cultural values as well. For conserving and managing wetlands technology, legislation, educational knowledge, action plan strategy and restoration practices are required. In order to address the human needs in the changing climate community-based adaptation approaches and wetland restoration, practices had been taken in almost every type of wetlands in Bangladesh. Therefore, Bangladesh now needs a comprehensive strategy and integrated system combining political, economic, social, technological approaches and institutional supports to address sustainable wetland restoration, conservation and the newly added crisis, climate change.

KIT(D816V) Induces SRC-Mediated Tyrosine Phosphorylation of MITF and Altered Transcription Program in Melanoma

DEFF Research Database (Denmark)

Phung, Bengt; Kazi, Julhash U; Lundby, Alicia

2017-01-01

The oncogenic D816V mutation of the KIT receptor is well characterized in systemic mastocytosis and acute myeloid leukemia. Although KIT(D816V) has been found in melanoma, its function and involvement in this malignancy is not understood. Here we show that KIT(D816V) induces tyrosine phosphorylat......The oncogenic D816V mutation of the KIT receptor is well characterized in systemic mastocytosis and acute myeloid leukemia. Although KIT(D816V) has been found in melanoma, its function and involvement in this malignancy is not understood. Here we show that KIT(D816V) induces tyrosine.......Implications: This study demonstrates that an oncogenic tyrosine kinase mutant, KIT(D816V), can alter the transcriptional program of the transcription factor MITF in melanoma Mol Cancer Res; 15(9); 1265-74. ©2017 AACR....

Radiation-induced malignant tumours: a specific cytogenetic profile?

International Nuclear Information System (INIS)

Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

1997-01-01

To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

Alterations and Abnormal Mitosis of Wheat Chromosomes Induced by Wheat-Rye Monosomic Addition Lines

Science.gov (United States)

Fu, Shulan; Yang, Manyu; Fei, Yunyan; Tan, Feiquan; Ren, Zhenglong; Yan, Benju; Zhang, Huaiyu; Tang, Zongxiang

2013-01-01

Background Wheat-rye addition lines are an old topic. However, the alterations and abnormal mitotic behaviours of wheat chromosomes caused by wheat-rye monosomic addition lines are seldom reported. Methodology/Principal Findings Octoploid triticale was derived from common wheat T. aestivum L. ‘Mianyang11’×rye S. cereale L. ‘Kustro’ and some progeny were obtained by the controlled backcrossing of triticale with ‘Mianyang11’ followed by self-fertilization. Genomic in situ hybridization (GISH) using rye genomic DNA and fluorescence in situ hybridization (FISH) using repetitive sequences pAs1 and pSc119.2 as probes were used to analyze the mitotic chromosomes of these progeny. Strong pSc119.2 FISH signals could be observed at the telomeric regions of 3DS arms in ‘Mianyang11’. However, the pSc119.2 FISH signals were disappeared from the selfed progeny of 4R monosomic addition line and the changed 3D chromosomes could be transmitted to next generation stably. In one of the selfed progeny of 7R monosomic addition line, one 2D chromosome was broken and three 4A chromosomes were observed. In the selfed progeny of 6R monosomic addition line, structural variation and abnormal mitotic behaviour of 3D chromosome were detected. Additionally, 1A and 4B chromosomes were eliminated from some of the progeny of 6R monosomic addition line. Conclusions/Significance These results indicated that single rye chromosome added to wheat might cause alterations and abnormal mitotic behaviours of wheat chromosomes and it is possible that the stress caused by single alien chromosome might be one of the factors that induced karyotype alteration of wheat. PMID:23936213

Toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.

Science.gov (United States)

Komaki, Yukako; Mariñas, Benito J; Plewa, Michael J

2014-10-07

Haloacetonitriles (HANs) are a chemical class of drinking water disinfection byproducts (DBPs) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. Treating Chinese hamster ovary (CHO) cells with monoHANs followed by the release from the chemical treatment resulted in the accumulation of abnormally high DNA content in cells over time (hyperploid). The potency for the cell cycle alteration followed the order: iodoacetonitrile (IAN) > bromoacetonitrile (BAN) ≫ chloroacetonitrile (CAN). Exposure to 6 μM IAN, 12 μM BAN and 900 μM CAN after 26 h post-treatment incubation resulted in DNA repair; however, subsequent cell cycle alteration effects were observed. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Enlarged cell size was observed after 52 h post-treatment incubation without the induction of cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggests that HAN treatment induced mitosis override, and that HAN-treated cells proceeded into S phase and directly into the next cell cycle. Cells with multiples genomes would result in aneuploidy (state of abnormal chromosome number and DNA content) at the next mitosis since extra centrosomes could compromise the assembly of bipolar spindles. There is accumulating evidence of a transient tetraploid state proceeding to aneuploidy in cancer progression. Biological self-defense systems to ensure genomic stability and to eliminate tetraploid cells exist in eukaryotic cells. A key tumor suppressor gene, p53, is oftentimes mutated in various types of human cancer. It is possible that HAN disruption of the normal cell cycle and the generation of aberrant cells with an abnormal number of

Activation of D2 autoreceptors alters cocaine-induced locomotion and slows down local field oscillations in the rat ventral tegmental area.

Science.gov (United States)

Koulchitsky, Stanislav; Delairesse, Charlotte; Beeken, Thom; Monteforte, Alexandre; Dethier, Julie; Quertemont, Etienne; Findeisen, Rolf; Bullinger, Eric; Seutin, Vincent

2016-09-01

Psychoactive substances affecting the dopaminergic system induce locomotor activation and, in high doses, stereotypies. Network mechanisms underlying the shift from an active goal-directed behavior to a "seemingly purposeless" stereotypic locomotion remain unclear. In the present study we sought to determine the relationships between the behavioral effects of dopaminergic drugs and their effects on local field potentials (LFPs), which were telemetrically recorded within the ventral tegmental area (VTA) of freely moving rats. We used the D2/D3 agonist quinpirole in a low, autoreceptor-selective (0.1 mg/kg, i.p.) and in a high (0.5 mg/kg, i.p.) dose, and a moderate dose of cocaine (10 mg/kg, i.p.). In the control group, power spectrum analysis revealed a prominent peak of LFP power in the theta frequency range during active exploration. Cocaine alone stimulated locomotion, but had no significant effect on the peak of the LFP power. In contrast, co-administration of low dose quinpirole with cocaine markedly altered the pattern of locomotion, from goal-directed exploratory behavior to recurrent motion resembling locomotor stereotypy. This behavioral effect was accompanied by a shift of the dominant theta power toward a significantly lower (by ∼15%) frequency. High dose quinpirole also provoked an increased locomotor activity with signs of behavioral stereotypies, and also induced a shift of the dominant oscillation frequency toward the lower range. These results demonstrate a correlation between the LFP oscillation frequency within the VTA and a qualitative aspect of locomotor behavior, perhaps due to a variable level of coherence of this region with its input or output areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of Hydrologic Alterations Caused by the Three Gorges Dam in the Middle and Lower Reaches of Yangtze River, China

Directory of Open Access Journals (Sweden)

Liuzhi Jiang

2014-05-01

Full Text Available Hydrologic regime plays a major role in structuring biotic diversity within river ecosystems by controlling key habitat conditions within the river channel and floodplain. Daily flow records from seven hydrological stations and the range of variability approach were utilized to investigate the variability and spatial pattern of the hydrologic alterations induced by the construction of the Three Gorges Dam (TGD in the middle and lower reaches of the Yangtze River, China. Results show that the impoundment of the TGD disturbed the hydrologic regime downstream and directly affected the streamflow variations. The rate of changes and the annual extreme conditions were more affected by the TGD, particularly the low-flow relevant parameters. The alterations in the hydrologic regime were mainly caused by the TGD storing water during early autumn and releasing water during winter and spring. The effects on spatial patterns decreased as the distance from the dam increased, which was mainly attributed to the inflows from large tributaries along the Yangtze River as well as the interaction with the two largest natural lakes (i.e., Dongting Lake and Poyang Lake. These hydrologic alterations not only break the natural balance of eco-flow regimes but also result in undesirable ecological effects, particularly in terms of habitat availability for the fish community.

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

Science.gov (United States)

Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

2012-12-19

This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

Directory of Open Access Journals (Sweden)

Malykhina Anna P

2012-12-01

Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

Science.gov (United States)

Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

2006-01-01

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

International Nuclear Information System (INIS)

Aluru, Neelakanteswar; Kuo, Elaine; Helfrich, Lily W.; Karchner, Sibel I.; Linney, Elwood A.; Pais, June E.; Franks, Diana G.

2015-01-01

DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Aluru, Neelakanteswar, E-mail: naluru@whoi.edu [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Kuo, Elaine [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Stanford University, 450 Serra Mall, Stanford, CA 94305 (United States); Helfrich, Lily W. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Northwestern University, 633 Clark St, Evanston, IL 60208 (United States); Karchner, Sibel I. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Linney, Elwood A. [Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710 (United States); Pais, June E. [New England Biolabs, 240 County Road, Ipswich, MA 01938 (United States); Franks, Diana G. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

2015-04-15

DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

Effect of Mucuna pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozotocin-induced diabetic rat.

Science.gov (United States)

Suresh, Sekar; Prakash, Seppan

2011-07-01

Erectile dysfunction is one of the major secondary complications of diabetes. Mucuna pruriens (M. pruriens), a leguminous plant identified for its antidiabetic, aphrodisiac, and fertility enhancing properties, has been the choice of Indian traditional medicine. The objective of the present study was to analyze the efficacy of M. pruriens on free radicals-mediated penile tissue alterations in hyperglycemic male rats. Methods.  Male albino rats were divided as group I (sham) control, group II (STZ) diabetes-induced (streptozotocin 60 mg/kg of body weight [bw] in 0.1 M citrate buffer), group III (STZ + MP) diabetic rats administered with 200 mg/kg bw of ethanolic extract of M. pruriens seed, group IV (STZ + SIL) diabetic rats administered with 5 mg/kg bw of sildenafil citrate, group V (sham + MP) administered with 200 mg/kg bw of extract alone, and group VI (sham + SIL) administered with 5 mg/kg bw of sildenafil citrate. The M. pruriens and sildenafil citrate were given (gavage) once daily for a period of 60 days. At the end of 60 days, the animals were sacrificed and subjected to analysis of reactive oxygen species levels, enzymic and nonenzymic antioxidant levels, levels of NOx, histological, and histomorphometrical study of penile tissue. Remedial use of M. pruriens seed extract on diabetes-induced erectile tissue damage. Significantly high levels of oxidative stress and low levels of antioxidants in the penile tissue seem to contribute to the increased collagen deposition and fibrosis of erectile tissue in STZ rats. Relatively, there was increased damage in STZ + SIL group. Supplementation of M. pruriens in STZ + MP group has revealed the potency to overcome oxidative stress, and good preservation of penile histoarchitecture.  The ethanolic extract of M. pruriens seed significantly recovered or protected erectile tissue from the oxidative stress-induced degeneration by its antioxidant potentials. These findings propound to serve mankind by the treatment of

Radiation-induced motility alterations in medulloblastoma cells

International Nuclear Information System (INIS)

Rieken, Stefan; Rieber, Juliane; Brons, Stephan

2015-01-01

Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α 5 . The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α 5 , which lead to increased cell adherence to extracellular matrix proteins. (author)

Exhaustive Exercise-induced Oxidative Stress Alteration of Erythrocyte Oxygen Release Capacity.

Science.gov (United States)

Xiong, Yanlian; Xiong, Yanlei; Wang, Yueming; Zhao, Yajin; Li, Yaojin; Ren, Yang; Wang, Ruofeng; Zhao, Mingzi; Hao, Yitong; Liu, Haibei; Wang, Xiang

2018-05-24

The aim of the present study is to explore the effect of exhaustive running exercise (ERE) in the oxygen release capacity of rat erythrocytes. Rats were divided into sedentary control (C), moderate running exercise (MRE) and exhaustive running exercise groups. The thermodynamics and kinetics properties of the erythrocyte oxygen release process of different groups were tested. We also determined the degree of band-3 oxidative and phosphorylation, anion transport activity and carbonic anhydrase isoform II(CAII) activity. Biochemical studies suggested that exhaustive running significantly increased oxidative injury parameters in TBARS and methaemoglobin levels. Furthermore, exhaustive running significantly decreased anion transport activity and carbonic anhydrase isoform II(CAII) activity. Thermodynamic analysis indicated that erythrocytes oxygen release ability also significantly increased due to elevated 2,3-DPG level after exhaustive running. Kinetic analysis indicated that exhaustive running resulted in significantly decreased T50 value. We presented evidence that exhaustive running remarkably impacted thermodynamics and kinetics properties of RBCs oxygen release. In addition, changes in 2,3-DPG levels and band-3 oxidation and phosphorylation could be the driving force for exhaustive running induced alterations in erythrocytes oxygen release thermodynamics and kinetics properties.

Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

Science.gov (United States)

Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

2015-10-01

Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

Lung scan alterations in congenital heart disease

Energy Technology Data Exchange (ETDEWEB)

Dietrich, R; Sanchez, J; Munoz, A; Lanaro, A E; Pico, A M

1975-04-01

This report analyzes the patterns in 54 lung scannings of 34 patients with altered pulmonary blood flow due to congenital heart disease. The technique and the results are presented. According to the images obtained, the patients are classified in three groups: Group I--normal distribution with more concentration of particles over the right lung and the bases. Group II--normal scannings found in left to right shunts unless there is pulmonary venous hypertension in which case the apex-base relationship was inverted. Group III--patients with right to left shunts of different types presenting various patterns according to severity, associated anomalies and palliative surgery. The hemodynamics created by cardiac defects and surgical procedures explain these alterations. This method is recommended in view of its advantages and accurate results.

Morphologic and functional alterations induced by low doses of mercuric chloride in the kidney OK cell line: ultrastructural evidence for an apoptotic mechanism of damage

International Nuclear Information System (INIS)

Carranza-Rosales, Pilar; Said-Fernandez, Salvador; Sepulveda-Saavedra, Julio; Cruz-Vega, Delia E.; Gandolfi, A. Jay

2005-01-01

Mercury produces acute renal failure in experimental animal models, but the mechanism of tubular injury has not completely been clarified. There is an increased interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelial cells. However, detailed studies of morpho-functional alterations induced by mercuric chloride in kidney cell lines are scarce. This work characterizes these alterations in OK cell cultures. Morphological alterations were profiled using light microscopy, transmission electron microscopy, and confocal microscopy, as well as mitochondrial functional assays in the cells exposed to low concentrations of HgCl 2 . At concentrations of 1 and 10 μM of HgCl 2 there were no morphological or ultrastructural alterations, but the mitochondrial function (MTT assay) and intracellular ATP content was increased, especially at longer incubation times (6 and 9 h). At 15 μM HgCl 2 , both the mitochondrial activity and the endogenous ATP decreased significantly. At this concentration the OK cells rounded up, had increased number of cytoplasmic vacuoles, and detached from the cell monolayer. At 15 μM HgCl 2 ultrastructural changes were characterized by dispersion of the ribosomes, dilatation of the cisterns of the rough endoplasmic reticulum, increase of number of cytoplasmic vacuoles, chromatin condensation, invaginations of the nuclear envelope, presence of cytoplasmic inclusion bodies, and alterations in the size and morphology of mitochondria. At 15 μM HgCl 2 apoptotic signs included membrane blebbing, chromatin condensation, mitochondrial alterations, apoptotic bodies, and nuclear envelope rupture. Using confocal microscopy and the mitochondrial specific dye MitoTracker Red, it was possible to establish qualitative changes induced by mercury on the mitochondrial membrane potential after incubation of the cells for 6 and 9 h with 15 μM HgCl 2 . This effect was not observed at short times

Experimentally induced tumors used for angiographic estimation of embolisation and cytostatic treatment

Energy Technology Data Exchange (ETDEWEB)

Strecker, E P; Kraus, W; Fiebig, H H; Kauffmann, G; Hauenstein, K H

1982-02-01

In 12 rats tumors have been induced chemically by intraperitoneal application of dimethylnitrosamine. This method is simple and reliable and the effect of tumor embolization can be followed easily. Thymus aplastic nude mice with transplanted human tumors deserve strict care. Tumor microangiograms of 48 animals demonstrate a close similarity with angiograms of corresponding human tumors. The vascular pattern does not alterate after several transplantations, after cytostatic therapy a slight hypervascularisation developes.

Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress.

Directory of Open Access Journals (Sweden)

Olivier Girard

Full Text Available Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C and CON (25°C conditions.Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting.Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001 and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05 temperatures, together with thermal comfort (P<0.001 were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001 and contact time (+3.2±2.4%; P<0.01 higher in HOT for the mean of sets 1-3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001, with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06. Mean vertical (-2.6±5.5%; P<0.01, horizontal (-9.1±4.4%; P<0.001 and resultant ground reaction forces (-3.0±2.8%; P<0.01 along with vertical stiffness (-12.9±2.3%; P<0.001 and leg stiffness (-8.4±2.7%; P<0.01 decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001, with lower propulsive power values in set 2 (-6.6%; P<0.05 in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise.Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations.

Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

Science.gov (United States)

Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

2017-01-01

Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

Science.gov (United States)

Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

2012-01-01

Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

Reconstruction of Laser-Induced Surface Topography from Electron Backscatter Diffraction Patterns.

Science.gov (United States)

Callahan, Patrick G; Echlin, McLean P; Pollock, Tresa M; De Graef, Marc

2017-08-01

We demonstrate that the surface topography of a sample can be reconstructed from electron backscatter diffraction (EBSD) patterns collected with a commercial EBSD system. This technique combines the location of the maximum background intensity with a correction from Monte Carlo simulations to determine the local surface normals at each point in an EBSD scan. A surface height map is then reconstructed from the local surface normals. In this study, a Ni sample was machined with a femtosecond laser, which causes the formation of a laser-induced periodic surface structure (LIPSS). The topography of the LIPSS was analyzed using atomic force microscopy (AFM) and reconstructions from EBSD patterns collected at 5 and 20 kV. The LIPSS consisted of a combination of low frequency waviness due to curtaining and high frequency ridges. The morphology of the reconstructed low frequency waviness and high frequency ridges matched the AFM data. The reconstruction technique does not require any modification to existing EBSD systems and so can be particularly useful for measuring topography and its evolution during in situ experiments.

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

Science.gov (United States)

Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

2013-11-01

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

Science.gov (United States)

Mimeault, Murielle; Batra, Surinder K

2013-01-01

Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue.

Science.gov (United States)

Klotz, J L; Brown, K R; Xue, Y; Matthews, J C; Boling, J A; Burris, W R; Bush, L P; Strickland, J R

2012-02-01

As part of a 2-yr study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined vasoconstrictive activities of 5-hydroxytryptamine (5HT), α-methylserotonin (ME5HT; a 5HT(2) receptor agonist), d-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from a high-endophyte-infected tall fescue pasture (HE) or a low-endophyte-infected mixed-grass (LE) pasture. Using the same pastures, Exp. 2 evaluated effects of grazing 2 levels of toxic endophyte-infected tall fescue on vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5HT(2A),( 2B), 5HT(1B), and 5HT(7) receptors, respectively. One-half of the steers in Exp. 2 were slaughtered immediately after removal from pasture, and the other one-half were fed finishing diets for >91 d before slaughter. For Exp. 1, maximal contractile intensities were greater (P 91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces functional alterations in blood vessels, as evidenced by reduced contractile capacity and altered serotonergic receptor activity. Experiment 2 demonstrated that grazing HE pastures alters vascular responses, which may be mediated through altered serotonin receptor activities, and these alterations may be ameliorated by the removal of ergot alkaloid exposure as demonstrated by the absence of differences in finished steers.

Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

Science.gov (United States)

Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

1978-02-28

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

International Nuclear Information System (INIS)

Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica; Shrivastava, Richa; Taneja, Isha; Hossain, Zakir; Mandalapu, Dhanaraju; Gayen, Jiaur R.; Wahajuddin, Muhammad; Sharma, Vishnu Lal; Trivedi, Arun K.; Sanyal, Sabyasachi; Bhadauria, Smrati; Godbole, Madan M.; Gupta, Sushil K.; Chattopadhyay, Naibedya

2016-01-01

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH) 2 vitamin D 3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast apoptosis

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

Energy Technology Data Exchange (ETDEWEB)

Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica [Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute - CDRI, Council of Scientific and Industrial Research (CSIR), Lucknow 226021 (India); Shrivastava, Richa [Division of Toxicology, CDRI-CSIR, Lucknow 226021 (India); Taneja, Isha; Hossain, Zakir [Pharmacokinetics and Metabolism Division, CDRI-CSIR, Lucknow 226021 (India); Mandalapu, Dhanaraju [Division of Medicinal and Process Chemistry, CDRI-CSIR, Lucknow 226021 (India); Gayen, Jiaur R.; Wahajuddin, Muhammad [Pharmacokinetics and Metabolism Division, CDRI-CSIR, Lucknow 226021 (India); Sharma, Vishnu Lal [Division of Medicinal and Process Chemistry, CDRI-CSIR, Lucknow 226021 (India); Trivedi, Arun K.; Sanyal, Sabyasachi [Division of Biochemistry, CDRI-CSIR, Lucknow 226021 (India); Bhadauria, Smrati [Division of Toxicology, CDRI-CSIR, Lucknow 226021 (India); Godbole, Madan M.; Gupta, Sushil K. [Department of Medical Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Chattopadhyay, Naibedya, E-mail: n_chattopadhyay@cdri.res.in [Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research - CSIR, Lucknow 226021 (India)

2016-03-15

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH){sub 2} vitamin D{sub 3} (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast

Linear disturbances on discontinuous permafrost: implications for thaw-induced changes to land cover and drainage patterns

International Nuclear Information System (INIS)

Williams, Tyler J; Quinton, William L; Baltzer, Jennifer L

2013-01-01

Within the zone of discontinuous permafrost, linear disturbances such as winter roads and seismic lines severely alter the hydrology, ecology, and ground thermal regime. Continued resource exploration in this environment has created a need to better understand the processes causing permafrost thaw and concomitant changes to the terrain and ground cover, in order to efficiently reduce the environmental impact of future exploration through the development of best management practices. In a peatland 50 km south of Fort Simpson, NWT, permafrost thaw and the resulting ground surface subsidence have produced water-logged linear disturbances that appear not to be regenerating permafrost, and in many cases have altered the land cover type to resemble that of a wetland bog or fen. Subsidence alters the hydrology of plateaus, developing a fill and spill drainage pattern that allows some disturbances to be hydrologically connected with adjacent wetlands via surface flow paths during periods of high water availability. The degree of initial disturbance is an important control on the extent of permafrost thaw and thus the overall potential recovery of the linear disturbance. Low impact techniques that minimize ground surface disturbance and maintain original surface topography by eliminating windrows are needed to minimize the impact of these linear disturbances. (letter)

Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

Energy Technology Data Exchange (ETDEWEB)

Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Sung, Kuo-Li Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412 (United States)

2013-11-08

Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.

Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

OpenAIRE

Almeida-Reis, Rafael; Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Lopes, Fernanda D. T. Q. S.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Leick, Edna A.; Oliva, Maria L. V.; Tibério, Iolanda F. L. C.

2017-01-01

Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.??C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respirator...

Protective effect of flax seed oil against radiation induced hematological alterations in mammals

International Nuclear Information System (INIS)

Sharma, Jyoti; Singh, Ritu; Goyal, P.K.; Singh, Seema

2014-01-01

Human beings are exposed to ionizing and non ionizing radiation from natural as well as manmade sources. Ionizing radiations are one of the predominant exogenous factors that have deleterious consequences to human life. Exposure to ionizing radiations damages the hematopoietic, gastrointestinal or central nervous systems, depending on radiation dose. Hence, there is an urgent need to prevent such deleterious effects caused due to ionizing radiations. Chemical protection involves the use of synthetic and natural products against planned radiation exposure. Medicinal plants are rich in antioxidants and their chemical constituents may be the potential source for radioprotective agents. Linum usitatissimum plant (family: Linaceae), source of flaxseed oil (FSO), is well known for its anticarcinogenic, antidiabetic, cardioprotector, antiulcer properties owing to the presence of various phytochemicals. The present study has been focused to find out the preventive action of flaxseed oil against radiation induced hematological and biochemical lesions in mammals. For this purpose, FSO (50μL/animal/day) was orally administered to Swiss albino mice for five days, prior to 6 Gy gamma radiation exposure. The animals were sacrificed on 1 st , 3 rd , 7 th , 15 th and 30 th day after irradiation. Radiation treated control group exhibited significant reduction in erythrocytes count, hemoglobin content, hematocrit value and total WBC count in peripheral blood. In contrast, pretreatment with FSO significantly increased all these blood constituents. Further, the antioxidant parameters such as reduced glutathione, catalase, and superoxide dismutase showed a significant elevation in FSO pretreated group which were reduced in irradiated control group. Similarly, radiation induced increase lipid peroxidation in blood was significantly inhibited after FSO treatment. The present results indicate that the flaxseed oil has the ability to debilitate the radiation induced adverse alterations in

Assessing urban context-induced change in individual activity travel patterns : case study of new railway station

NARCIS (Netherlands)

Arentze, T.A.; Borgers, A.W.J.; Ponjé, M.M.W.; Stams, A.; Timmermans, H.J.P.

2001-01-01

Findings are reported of selective descriptive analyses that were conducted to examine whether the opening of a new railway station had induced any changes in the activity travel patterns of a panel of house holds. In particular, changes in choices related to trip generation, trip chaining,

Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

International Nuclear Information System (INIS)

Ganesan, Shanthi; Nteeba, Jackson; Keating, Aileen F.

2015-01-01

The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility

Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

Energy Technology Data Exchange (ETDEWEB)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

2015-01-01

The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility.

Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

Science.gov (United States)

Molina, S J; Capani, F; Guelman, L R

2016-04-01

It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.

Science.gov (United States)

Castillon, Charlotte; Lunion, Steeve; Desvignes, Nathalie; Hanauer, André; Laroche, Serge; Poirier, Roseline

2018-07-01

Adult neurogenesis is involved in certain hippocampus-dependent cognitive functions and is linked to psychiatric diseases including intellectual disabilities. The Coffin-Lowry syndrome (CLS) is a developmental disorder caused by mutations in the Rsk2 gene and characterized by intellectual disabilities associated with growth retardation. How RSK2-deficiency leads to cognitive dysfunctions in CLS is however poorly understood. Here, using Rsk2 Knock-Out mice, we characterized the impact of RSK2 deficiency on adult hippocampal neurogenesis in vivo. We report that the absence of RSK2 does not affect basal proliferation, differentiation and survival of dentate gyrus adult-born neurons but alters the maturation progression of young immature newborn neurons. Moreover, when RSK2-deficient mice were submitted to spatial learning, in contrast to wild-type mice, proliferation of adult generated neurons was decreased and no pro-survival effect of learning was observed. Thus, learning failed to recruit a selective population of young newborn neurons in association with deficient long-term memory recall. Given the proposed role of the dentate gyrus and of adult-generated newborn neurons in hippocampal-dependent pattern separation function, we explored this function in a delayed non-matching to place task and in an object-place pattern separation task and report severe deficits in spatial pattern separation in Rsk2-KO mice. Together, this study reveals a previously unknown role for RSK2 in the early stages of maturation and learning-dependent involvement of adult-born dentate gyrus neurons. These alterations associated with a deficit in the ability of RSK2-deficient mice to finely discriminate relatively similar spatial configurations, may contribute to cognitive dysfunction in CLS. Copyright © 2018 Elsevier Inc. All rights reserved.

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

Science.gov (United States)

Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-11-01

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Field effect transistors and photodetectors based on nanocrystalline graphene derived from electron beam induced carbonaceous patterns

International Nuclear Information System (INIS)

Kurra, Narendra; Bhadram, Venkata Srinu; Narayana, Chandrabhas; Kulkarni, G U

2012-01-01

We describe a transfer-free method for the fabrication of nanocrystalline graphene (nc-graphene) on SiO 2 substrates directly from patterned carbonaceous deposits. The deposits were produced from the residual hydrocarbons present in the vacuum chamber without any external source by using an electron beam induced carbonaceous deposition (EBICD) process. Thermal treatment under vacuum conditions in the presence of Ni catalyst transformed the EBIC deposit into nc-graphene patterns, confirmed using Raman and TEM analysis. The nc-graphene patterns have been employed as an active p-type channel material in a field effect transistor (FET) which showed a hole mobility of ∼90 cm 2 V −1 s −1 . The nc-graphene also proved to be suitable material for IR detection. (paper)

Direct-write maskless lithography using patterned oxidation of Si-substrate Induced by femtosecond laser pulses

Science.gov (United States)

Kiani, Amirkianoosh; Venkatakrishnan, Krishnan; Tan, Bo

2013-03-01

In this study we report a new method for direct-write maskless lithography using oxidized silicon layer induced by high repetition (MHz) ultrafast (femtosecond) laser pulses under ambient condition. The induced thin layer of predetermined pattern can act as an etch stop during etching process in alkaline etchants such as KOH. The proposed method can be leading to promising solutions for direct-write maskless lithography technique since the proposed method offers a higher degree of flexibility and reduced time and cost of fabrication which makes it particularly appropriate for rapid prototyping and custom scale manufacturing. A Scanning Electron Microscope (SEM), Micro-Raman, Energy Dispersive X-ray (EDX), optical microscope and X-ray diffraction spectroscopy (XRD) were used to evaluate the quality of oxidized layer induced by laser pulses.

Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.J.; Bennett, E.L.

1979-01-01

The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

Science.gov (United States)

Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

1997-12-18

Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

Science.gov (United States)

Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

2018-08-01

The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences.

Science.gov (United States)

Philips, Mari-Anne; Abramov, Urho; Lilleväli, Kersti; Luuk, Hendrik; Kurrikoff, Kaido; Raud, Sirli; Plaas, Mario; Innos, Jürgen; Puussaar, Triinu; Kõks, Sulev; Vasar, Eero

2010-02-11

Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences.

Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype?

Science.gov (United States)

Niller, Hans Helmut; Minarovits, Janos

2012-01-01

EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is indispensable for the maintenance of the viral episomes in latently infected cells. EBNA1 may induce genetic alterations by upregulating cellular recombinases, production of reactive oxygen species (ROS) and affecting p53 levels and function. All these changes may contribute to tumorigenesis. In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors. Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. Local DNA demethylation and nucleosome rearrangement mark active promoters and enhancers. In addition, EBNA1 and FoxA, when associated with mitotic chromatin may “bookmark” active genes and ensure their reactivation in postmitotic cells (epigenetic memory). We speculate that DNA looping induced by EBNA1-EBNA1 interactions may reorganize the cellular genome. Such chromatin loops, sustained in mitotic chromatin similarly to the long-distance interactions mediated by the insulator protein CTCF, may also mediate the epigenetic inheritance of gene expression patterns. We suggest that EBNA1 has the potential to induce patho-epigenetic alterations contributing to tumorigenesis. PMID:25436603

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

Science.gov (United States)

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Sex influences in behavior and brain inflammatory and oxidative alterations in mice submitted to lipopolysaccharide-induced inflammatory model of depression.

Science.gov (United States)

Mello, Bruna Stefânia Ferreira; Chaves Filho, Adriano José Maia; Custódio, Charllyany Sabino; Cordeiro, Rafaela Carneiro; Miyajima, Fabio; de Sousa, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Macedo, Danielle

2018-07-15

Peripheral inflammation induced by lipopolysaccharide (LPS) causes a behavioral syndrome with translational relevance for depression. This mental disorder is twice more frequent among women. Despite this, the majority of experimental studies investigating the neurobiological effects of inflammatory models of depression have been performed in males. Here, we sought to determine sex influences in behavioral and oxidative changes in brain regions implicated in the pathophysiology of mood disorders (hypothalamus, hippocampus and prefrontal cortex - PFC) in adult mice 24 h post LPS challenge. Myeloperoxidase (MPO) activity and interleukin (IL)-1β levels were measured as parameters of active inflammation, while reduced glutathione (GSH) and lipid peroxidation as parameters of oxidative imbalance. We observed that male mice presented behavioral despair, while females anxiety-like alterations. Both sexes were vulnerable to LPS-induced anhedonia. Both sexes presented increased MPO activity in the PFC, while male only in the hippocampus. IL-1β increased in the PFC and hypothalamus of animals of both sexes, while in the hippocampus a relative increase of this cytokine in males compared to females was detected. GSH levels were decreased in all brain areas investigated in animals of both sexes, while increased lipid peroxidation was observed in the hypothalamus of females and in the hippocampus of males after LPS exposure. Therefore, the present study gives additional evidence of sex influence in LPS-induced behavioral alterations and, for the first time, in the oxidative changes in brain areas relevant for mood regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease.

Science.gov (United States)

Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; McBirney, Margaux; Nilsson, Eric; Klukovich, Rachel; Xie, Yeming; Tang, Chong; Yan, Wei; Skinner, Michael K

2018-04-01

Epigenetic transgenerational inheritance of disease and phenotypic variation can be induced by several toxicants, such as vinclozolin. This phenomenon can involve DNA methylation, non-coding RNA (ncRNA) and histone retention, and/or modification in the germline (e.g. sperm). These different epigenetic marks are called epimutations and can transmit in part the transgenerational phenotypes. This study was designed to investigate the vinclozolin-induced concurrent alterations of a number of different epigenetic factors, including DNA methylation, ncRNA, and histone retention in rat sperm. Gestating females (F0 generation) were exposed transiently to vinclozolin during fetal gonadal development. The directly exposed F1 generation fetus, the directly exposed germline within the fetus that will generate the F2 generation, and the transgenerational F3 generation sperm were studied. DNA methylation and ncRNA were altered in each generation rat sperm with the direct exposure F1 and F2 generations being distinct from the F3 generation epimutations. Interestingly, an increased number of differential histone retention sites were found in the F3 generation vinclozolin sperm, but not in the F1 or F2 generations. All three different epimutation types were affected in the vinclozolin lineage transgenerational sperm (F3 generation). The direct exposure generations (F1 and F2) epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene pathways associated with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Our results show that the three different types of epimutations are involved and integrated in the mediation of the epigenetic transgenerational inheritance phenomenon.

Specitic gene alterations in radiation-induced tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Ahn, Joo Mee; Kang, Chang Mo; Lee, Seung Sook; Cho, Chul Koo; Bae, Sang Woo; Lee, Su Jae; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2004-07-01

To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and -R4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R1 and -R4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while 2 CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R1 or R-4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R1 and R4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and R4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.

Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

Directory of Open Access Journals (Sweden)

McIver Lauren J

2009-12-01

Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

Directory of Open Access Journals (Sweden)

Ashish Srivastava

2017-07-01

Full Text Available A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L. plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV and Ageratum leaf curl betasatellite (ALCB, respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.

Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats; Alterations de la motricite digestive associees aux processus inflammatoires induits par les rayonnements ionisants chez le rat

Energy Technology Data Exchange (ETDEWEB)

Picard, C

2000-12-01

Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT{sub 3} receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

Alteration of foliar flavonoid chemistry induced by enhanced UV-B radiation in field-grown Pinus ponderosa, Quercus rubra and Pseudotsuga menziesii.

Science.gov (United States)

Warren, Jeffrey M; Bassman, John H; Mattinson, D Scott; Fellman, John K; Edwards, Gerald E; Robberecht, Ronald

2002-03-01

Chromatographic analyses of foliage from several tree species illustrate the species-specific effects of UV-B radiation on both quantity and composition of foliar flavonoids. Pinus ponderosa, Quercus rubra and Pseudotsuga menziesii were field-grown under modulated ambient (1x) and enhanced (2x) biologically effective UV-B radiation. Foliage was harvested seasonally over a 3-year period, extracted, purified and the flavonoid fraction applied to a mu Bondapak/C(18) column HPLC system sampling at 254 nm. Total flavonoid concentrations in Quercus rubra foliage were more than twice (leaf area basis) that of the other species; Pseudotsuga menziesii foliage had intermediate levels and P. ponderosa had the lowest concentrations of total flavonoids. No statistically significant UV-B radiation-induced effects were found in total foliar flavonoid concentrations for any species; however, concentrations of specific compounds within each species exhibited significant treatment effects. Higher (but statistically insignificant) levels of flavonoids were induced by UV-B irradiation in 1- and 2-year-old P. ponderosa foliage. Total flavonoid concentrations in 2-year-old needles increased by 50% (1x ambient UV-B radiation) or 70% (2x ambient UV-B radiation) from that of 1-year-old tissue. Foliar flavonoids of Q. rubra under enhanced UV-B radiation tended to shift from early-eluting compounds to less polar flavonoids eluting later. There were no clear patterns of UV-B radiation effects on 1-year-old P. menziesii foliage. However, 2-year-old tissue had slightly higher foliar flavonoids under the 2x UV-B radiation treatment compared to ambient levels. Results suggest that enhanced UV-B radiation will alter foliar flavonoid composition and concentrations in forest tree species, which could impact tissue protection, and ultimately, competition, herbivory or litter decomposition.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: Relevance of a well-balanced UVA/UVB protection

Directory of Open Access Journals (Sweden)

Françoise Bernerd

2012-01-01

Full Text Available Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

Science.gov (United States)

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

International Nuclear Information System (INIS)

Yano, Claudia L; Ventrucci, Gislaine; Field, William N; Tisdale, Michael J; Gomes-Marcondes, Maria Cristina C

2008-01-01

Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C 2 C 12 muscle cells. WF decreased the viability of C 2 C 12 myotubes, especially at concentrations of 20–25 μg.mL -1 . There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

Directory of Open Access Journals (Sweden)

Tisdale Michael J

2008-01-01

Full Text Available Abstract Background Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. Methods In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF, which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. Results WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. Conclusion These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

Different zinc sensitivity of Brassica organs is accompanied by distinct responses in protein nitration level and pattern.

Science.gov (United States)

Feigl, Gábor; Kolbert, Zsuzsanna; Lehotai, Nóra; Molnár, Árpád; Ördög, Attila; Bordé, Ádám; Laskay, Gábor; Erdei, László

2016-03-01

Zinc is an essential microelement, but its excess exerts toxic effects in plants. Heavy metal stress can alter the metabolism of reactive oxygen (ROS) and nitrogen species (RNS) leading to oxidative and nitrosative damages; although the participation of these processes in Zn toxicity and tolerance is not yet known. Therefore this study aimed to evaluate the zinc tolerance of Brassica organs and the putative correspondence of it with protein nitration as a relevant marker for nitrosative stress. Both examined Brassica species (B. juncea and B. napus) proved to be moderate Zn accumulators; however B. napus accumulated more from this metal in its organs. The zinc-induced damages (growth diminution, altered morphology, necrosis, chlorosis, and the decrease of photosynthetic activity) were slighter in the shoot system of B. napus than in B. juncea. The relative zinc tolerance of B. napus shoot was accompanied by moderate changes of the nitration pattern. In contrast, the root system of B. napus suffered more severe damages (growth reduction, altered morphology, viability loss) and slighter increase in nitration level compared to B. juncea. Based on these, the organs of Brassica species reacted differentially to excess zinc, since in the shoot system modification of the nitration pattern occurred (with newly appeared nitrated protein bands), while in the roots, a general increment in the nitroproteome could be observed (the intensification of the same protein bands being present in the control samples). It can be assumed that the significant alteration of nitration pattern is coupled with enhanced zinc sensitivity of the Brassica shoot system and the general intensification of protein nitration in the roots is attached to relative zinc endurance. Copyright © 2015 Elsevier Inc. All rights reserved.

Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus

International Nuclear Information System (INIS)

Baranowska-Bosiacka, I.; Strużyńska, L.; Gutowska, I.; Machalińska, A.; Kolasa, A.; Kłos, P.; Czapski, G.A.; Kurzawski, M.; Prokopowicz, A.; Marchlewicz, M.

2013-01-01

Highlights: ► Pre- and neonatal Pb exposure decreased the number of hippocampal neurons. ► Lead caused ultrastructural alterations in CA1 region of hippocampus. ► Hippocampus is highly vulnerable to low level perinatal Pb exposure. ► Lead decreased BDNF level in the developing brain. ► Decreased Bax/Bcl2 ratio may protect hippocampus against Pb-induced apoptosis. -- Abstract: The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb) may intensify or inhibit apoptosis or necroptosis in the developing rat brain. Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring; the control group received distilled water. During the feeding of pups, mothers from the experimental group were still receiving PbAc. Pups were weaned at postnatal day 21 and the young rats of both groups then received only distilled water until postnatal day 28. This treatment protocol resulted in a concentration of Pb in rat offspring whole blood (Pb-B) below the threshold of 10 μg/dL, considered safe for humans.We studied Casp-3 activity and expression, AIF nuclear translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein expression as well as BDNF concentration in selected structures of the rat brain: forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic examinations showed alterations in hippocampal neurons.Our data shows that pre- and neonatal exposure of rats to Pb, leading to Pb-B below 10 μg/dL, can decrease the number of hippocampus neurons, occurring concomitantly with ultrastructural alterations in this region. We observed no morphological or molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF translocation to nucleus) in young brains, despite the reduced levels of BDNF. The potential protective factor against apoptosis was probably the decreased Bax/Bcl-2 ratio, which requires further investigation. Our

The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma

Directory of Open Access Journals (Sweden)

Stafford Phillip

2010-09-01

Full Text Available Abstract Background Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia. Methods Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet. Results Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4. Conclusions Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

Time-dependent patterns in quasivertical cylindrical binary convection

Science.gov (United States)

Alonso, Arantxa; Mercader, Isabel; Batiste, Oriol

2018-02-01

This paper reports on numerical investigations of the effect of a slight inclination α on pattern formation in a shallow vertical cylindrical cell heated from below for binary mixtures with a positive value of the Soret coefficient. By using direct numerical simulation of the three-dimensional Boussinesq equations with Soret effect in cylindrical geometry, we show that a slight inclination of the cell in the range α ≈0.036 rad =2∘ strongly influences pattern selection. The large-scale shear flow (LSSF) induced by the small tilt of gravity overcomes the squarelike arrangements observed in noninclined cylinders in the Soret regime, stratifies the fluid along the direction of inclination, and produces an enhanced separation of the two components of the mixture. The competition between shear effects and horizontal and vertical buoyancy alters significantly the dynamics observed in noninclined convection. Additional unexpected time-dependent patterns coexist with the basic LSSF. We focus on an unsual periodic state recently discovered in an experiment, the so-called superhighway convection state (SHC), in which ascending and descending regions of fluid move in opposite directions. We provide numerical confirmation that Boussinesq Navier-Stokes equations with standard boundary conditions contain the essential ingredients that allow for the existence of such a state. Also, we obtain a persistent heteroclinic structure where regular oscillations between a SHC pattern and a state of nearly stationary longitudinal rolls take place. We characterize numerically these time-dependent patterns and investigate the dynamics around the threshold of convection.

Sub-micron magnetic patterns and local variations of adhesion force induced in non-ferromagnetic amorphous steel by femtosecond pulsed laser irradiation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Huiyan; Feng, Yuping [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); Nieto, Daniel [Microoptics and GRIN Optics Group, Applied Physics Department, University of Santiago de Compostela, E15782 Santiago de Compostela (Spain); García-Lecina, Eva [Unidad de Superficies Metálicas, IK4-CIDETEC, E20009 Donostia-San Sebastián Gipuzkoa (Spain); Mcdaniel, Clare [National Centre for Laser Applications, School of Physics, National University of Ireland, Galway (Ireland); Díaz-Marcos, Jordi [Unitat de Tècniques Nanomètriques, Centres Científics i Tecnològics, Universitat de Barcelona, E08028 Barcelona (Spain); Flores-Arias, María Teresa [Microoptics and GRIN Optics Group, Applied Physics Department, University of Santiago de Compostela, E15782 Santiago de Compostela (Spain); O’Connor, Gerard M. [National Centre for Laser Applications, School of Physics, National University of Ireland, Galway (Ireland); Baró, Maria Dolors [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); Pellicer, Eva, E-mail: eva.pellicer@uab.cat [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); and others

2016-05-15

Highlights: • Formation of ripples after femtosecond pulsed laser irradiation (FSPLI) of metallic glass was studied. • Magnetic patterning at the surface of non-ferromagnetic amorphous steel was induced by FSPLI. • The origin of the generated ferromagnetism is the laser-induced devitrification. - Abstract: Periodic ripple and nanoripple patterns are formed at the surface of amorphous steel after femtosecond pulsed laser irradiation (FSPLI). Formation of such ripples is accompanied with the emergence of a surface ferromagnetic behavior which is not initially present in the non-irradiated amorphous steel. The occurrence of ferromagnetic properties is associated with the laser-induced devitrification of the glassy structure to form ferromagnetic (α-Fe and Fe{sub 3}C) and ferrimagnetic [(Fe,Mn){sub 3}O{sub 4} and Fe{sub 2}CrO{sub 4}] phases located in the ripples. The generation of magnetic structures by FSPLI turns out to be one of the fastest ways to induce magnetic patterning without the need of any shadow mask. Furthermore, local variations of the adhesion force, wettability and nanomechanical properties are also observed and compared to those of the as-cast amorphous alloy. These effects are of interest for applications (e.g., biological, magnetic recording, etc.) where both ferromagnetism and tribological/adhesion properties act synergistically to optimize material performance.

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

International Nuclear Information System (INIS)

Barillet, Sabrina; Larno, Valerie; Floriani, Magali; Devaux, Alain; Adam-Guillermin, Christelle

2010-01-01

Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

Energy Technology Data Exchange (ETDEWEB)

Barillet, Sabrina, E-mail: sabrina.barillet@free.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Larno, Valerie, E-mail: valerie.larno@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Floriani, Magali, E-mail: magali.floriani@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [INRA, EFPA Department, 54280, Champenoux and Environmental Science Laboratory, ENTPE, 69518 Vaulx en Velin cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France)

2010-11-01

Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

Patterns of Sympathetic Responses Induced by Different Stress Tasks

Science.gov (United States)

Fechir, M; Schlereth, T; Purat, T; Kritzmann, S; Geber, C; Eberle, T; Gamer, M; Birklein, F

2008-01-01

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction. Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research. PMID:19018304

Alteration of protein patterns in black rock inhabiting fungi as a response to different temperatures

Science.gov (United States)

Tesei, Donatella; Marzban, Gorji; Zakharova, Kristina; Isola, Daniela; Selbmann, Laura; Sterflinger, Katja

2012-01-01

Rock inhabiting fungi are among the most stress tolerant organisms on Earth. They are able to cope with different stressors determined by the typical conditions of bare rocks in hot and cold extreme environments. In this study first results of a system biological approach based on two-dimensional protein profiles are presented. Protein patterns of extremotolerant black fungi – Coniosporium perforans, Exophiala jeanselmei – and of the extremophilic fungus – Friedmanniomyces endolithicus – were compared with the cosmopolitan and mesophilic hyphomycete Penicillium chrysogenum in order to follow and determine changes in the expression pattern under different temperatures. The 2D protein gels indicated a temperature dependent qualitative change in all the tested strains. Whereas the reference strain P. chrysogenum expressed the highest number of proteins at 40 °C, thus exhibiting real signs of temperature induced reaction, black fungi, when exposed to temperatures far above their growth optimum, decreased the number of proteins indicating a down-regulation of their metabolism. Temperature of 1 °C led to an increased number of proteins in all of the analysed strains, with the exception of P. chrysogenum. These first results on temperature dependent reactions in rock inhabiting black fungi indicate a rather different strategy to cope with non-optimal temperature than in the mesophilic hyphomycete P. chrysogenum. PMID:22862921

Cell patterning on poly(sodium 4-styrenesulfonate)-patterned fluoropolymer substrate

Energy Technology Data Exchange (ETDEWEB)

Kim, Wan-Joong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Jung, Chang-Hee; Hwang, In-Tae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Jung, Chan-Hee, E-mail: jch@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Choi, Jae-Hak, E-mail: jaehakchoi@cnu.ac.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Hong, Sung-Kwon [Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of)

2013-10-15

Highlights: •PFA films were functionalized by ion-beam induced surface graft polymerization. •Poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films were prepared. •Well-organized cell patterns were obtained on PSS-patterned PFA films. •This method is useful to fabricate bio-platforms for cell-based biodevices. -- Abstract: The surface functionalization of bio-inert fluoropolymer films through ion beam-induced surface graft polymerization was investigated to control the cellular behavior. The surface of poly(tetrafluoroethylene-co-perfluoropropl vinyl ether) (PFA) films was selectively activated by 150 keV H{sup +} ion implantation in the presence of a pattern mask and sodium 4-styrenesulfonate (SS) was then graft polymerized onto the implanted PFA films to form hydrophilic poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films. The surface of the resulting PSS-patterned PFA films was investigated in terms of the degree of graft polymerization, chemical structure, chemical composition, wettability, and morphology. The analytical results revealed that PSS was selectively grafted onto the implanted regions of the PFA films. Furthermore, in vitro cell culture on the PSS-patterned PFA films exhibited a preferential adhesion and growth of cells onto the PSS-grafted regions, resulting in well-organized 100 μm cell patterns.

Cell patterning on poly(sodium 4-styrenesulfonate)-patterned fluoropolymer substrate

International Nuclear Information System (INIS)

Kim, Wan-Joong; Jung, Chang-Hee; Hwang, In-Tae; Jung, Chan-Hee; Choi, Jae-Hak; Hong, Sung-Kwon

2013-01-01

Highlights: •PFA films were functionalized by ion-beam induced surface graft polymerization. •Poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films were prepared. •Well-organized cell patterns were obtained on PSS-patterned PFA films. •This method is useful to fabricate bio-platforms for cell-based biodevices. -- Abstract: The surface functionalization of bio-inert fluoropolymer films through ion beam-induced surface graft polymerization was investigated to control the cellular behavior. The surface of poly(tetrafluoroethylene-co-perfluoropropl vinyl ether) (PFA) films was selectively activated by 150 keV H + ion implantation in the presence of a pattern mask and sodium 4-styrenesulfonate (SS) was then graft polymerized onto the implanted PFA films to form hydrophilic poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films. The surface of the resulting PSS-patterned PFA films was investigated in terms of the degree of graft polymerization, chemical structure, chemical composition, wettability, and morphology. The analytical results revealed that PSS was selectively grafted onto the implanted regions of the PFA films. Furthermore, in vitro cell culture on the PSS-patterned PFA films exhibited a preferential adhesion and growth of cells onto the PSS-grafted regions, resulting in well-organized 100 μm cell patterns

PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

Science.gov (United States)

Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

2014-01-01

Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

Sulphur depletion altered somatic embryogenesis in Theobroma ...

African Journals Online (AJOL)

Somatic embryogenesis is a useful tool for Theobroma cacao improvement and propagation. Depending on culture medium composition, different morphogenetic structures (including somatic embryo) occur in response to alteration of genes expression patterns and biochemical changes. The effect of SO42- ion deficiency ...

Cytosine arabinoside enhancement of gamma irradiation induced mutations in human T-lymphocytes

International Nuclear Information System (INIS)

O'Neill, J.P.; Sullivan, L.M.; Hunter, T.C.; Nicklas, J.A.

1991-01-01

The frequency of 6-thioguanine resistant (TGr) mutants induced in human G0 phase T-lymphocytes by 200 cGy of gamma irradiation is greatly enhanced by incubation with cytosine arabinoside (ara-C) after irradiation. The mutant frequency increased with increasing incubation time in ara-C for up to 2 hr. This mutation induction required a phenotypic expression time of 5-8 days mass culture growth, similar to that found with mutants induced by 300 cGy of irradiation alone. Southern blot analysis of 40 isolated mutant clones revealed 8 independent mutations by T-cell receptor (TCR) gene rearrangement patterns. Four of these eight showed hprt gene structural alterations (0.50). An alternative method to allow phenotypic expression was developed to minimize the isolation of hprt/TCR sibling mutants. The use of in situ expression in the microtiter dish wells resulted in the isolation of 17 independent mutations in 19 mutant clones. Ten of these 17 mutations showed hprt structural alterations (0.59). The high fraction of mutations involving structural alterations detected by Southern blot analysis is consistent with the known induction of chromosome aberrations by irradiation plus ara-C treatment. We propose that both the increase in Mf and the increase in the incidence of hprt gene structural alterations are due to the accumulation of strand breaks in repairing regions of DNA under these conditions of ara-C induced inhibition of repair. We further propose that upon release of the ara-C inhibition, these repairing regions can interact to yield both gene mutations and chromosome aberrations

Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood.

Science.gov (United States)

Solomon, Olivia; Yousefi, Paul; Huen, Karen; Gunier, Robert B; Escudero-Fung, Maria; Barcellos, Lisa F; Eskenazi, Brenda; Holland, Nina

2017-07-01

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican-American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb-p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di-(2-ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398-410, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Exercise-induced rib stress fractures: potential risk factors related to thoracic muscle co-contraction and movement pattern

DEFF Research Database (Denmark)

Vinther-Knudsen, Archibald; Kanstrup, I-L; Christiansen, E

2006-01-01

The etiology of exercise-induced rib stress fractures (RSFs) in elite rowers is unclear. The purpose of the study was to investigate thoracic muscle activity, movement patterns and muscle strength in elite rowers. Electromyographic (EMG) and 2-D video analysis were performed during ergometer rowing...