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Sample records for aberrant crypt foci

  1. Diet, aberrant crypt foci and colorectal cancer.

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    Bruce, W R; Archer, M C; Corpet, D E; Medline, A; Minkin, S; Stamp, D; Yin, Y; Zhang, X M

    1993-11-01

    We have used the aberrant crypt focus (ACF) assay to test and develop hypotheses linking diet and colon cancer. The hypotheses were suggested by epidemiological studies that identified possible dietary factors associated with colorectal cancer risk. The ACF assay was used to quantitate the effect of the dietary factors on the initiation and growth of these putative precursors of colon cancers in experimental animals. Using this approach we have developed 3 new hypotheses for the role of diet in colorectal cancer. These are (1) a risk associated with 5-hydroxymethyl-2-furaldehyde in caramelized sugar, (2) a risk associated with some factor in thermolyzed casein, and (3) a risk associated with single nutrient boluses of sucrose and fructose. The importance of these hypotheses has still to be tested in long term carcinogenesis experiments, in analytic epidemiology studies and then, perhaps, in intervention trials.

  2. Variational image segmentation for endoscopic human colonic aberrant crypt foci.

    Science.gov (United States)

    Figueiredo, Isabel N; Figueiredo, Pedro N; Stadler, Georg; Ghattas, Omar; Araujo, Adérito

    2010-04-01

    The aim of this paper is to introduce a variational image segmentation method for assessing the aberrant crypt foci (ACF) in the human colon captured in vivo by endoscopy. ACF are thought to be precursors for colorectal cancer, and therefore their early detection may play an important clinical role. We enhance the active contours without edges model of Chan and Vese to account for the ACF's particular structure. We employ level sets to represent the segmentation boundaries and discretize in space by finite elements and in (artificial) time by finite differences. The approach is able to identify the ACF, their boundaries, and some of the internal crypts' orifices.

  3. Aberrant crypt foci and microadenoma as markers for colon cancer.

    Science.gov (United States)

    Archer, M C; Bruce, W R; Chan, C C; Corpet, D E; Medline, A; Roncucci, L; Stamp, D; Zhang, X M

    1992-11-01

    Foci of aberrant crypts similar to those seen in experimental animals exposed to colon carcinogens have been identified and quantified on the mucosal surface of fixed resections of human colon after methylene blue staining. Many of the foci in humans showed dysplasia on histologic examination and were considered to be microadenoma (MA). These lesions may be precursors for adenomatous polyps and colorectal cancer. Rats and mice initiated with azoxymethane, then fed diets containing sucrose or casein heated at 180 degrees C to stimulate normal cooking conditions, had three to five times more large MA after 100 days than controls. Thus, cooked sugar and protein contain promoters of the growth of colonic MA. 5-Hydroxymethylfuraldehyde was identified as a promoter in cooked sugar.

  4. Promotion of aberrant crypt foci and cancer in rat colon by thermolyzed protein.

    Science.gov (United States)

    Zhang, X M; Stamp, D; Minkin, S; Medline, A; Corpet, D E; Bruce, W R; Archer, M C

    1992-07-01

    We have previously shown that thermolyzed protein (casein) cooked with fat in the diet of the rat promotes the growth of aberrant crypt foci (putative precursors of colon cancer) assessed at 100 days. To determine how thermolysis affects this promotion, we examined thermolysis conditions, quantity of thermolyzed protein in the diet, and duration of thermolysis. To determine whether the previous finding of promotion of aberrant crypt foci corresponds to promotion of cancers assessed much later, we carried out promotion studies until colon cancers appeared. F344 rats were given an initiating dose of azoxymethane and were then randomly allocated to groups receiving diets differing in their quantity and quality of casein. The groups were examined for aberrant crypt foci and tumors in the colon. Aberrant crypt foci were promoted by diets containing thermolyzed casein (180 degrees C, 2 hours). Promotion increased with increasing level of thermolyzed casein in the diet (to 20%) and with increasing thermolysis time (to 4 hours). The number of animals with polyps and cancers was higher in the animals receiving thermolyzed protein (2 hours), 16/23 versus 9/26 (P less than .05) and 10/26 versus 3/27 (P less than .05), respectively. The number of aberrant crypts per focus and the number of large aberrant crypt foci were higher in the tumor-bearing animals. Thermolyzed casein promotes early colonic precursor lesions in a dose-dependent and thermolysis time-dependent manner; thermolyzed casein also promotes colon cancer. The promoter formed on thermolysis could be involved in colon cancers associated with diets cooked at elevated temperatures, such as can occur with high-fat diets.

  5. The ability of two cooked food mutagens to induce aberrant crypt foci in mice

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1997-01-01

    The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet, In the present study two food-borne initiators, 2-amino-3-methyl-imidazo [4,5-f]quinoline (IQ) and 2......-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used, To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses, Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP, Two additional groups were given...... induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ, The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens, If cooked food mutagens...

  6. Suppression of azoxymethane-induced colonic aberrant crypt foci by a nitric oxide synthase inhibitor.

    Science.gov (United States)

    Kawamori, T; Takahashi, M; Watanabe, K; Ohta, T; Nakatsugi, S; Sugimura, T; Wakabayashi, K

    2000-01-01

    Nitric oxide synthase (NOS), an important bioregulator of a variety of biological processes, is overexpressed in colonic tumors of humans and rodents. In this study, effects of L-N(G)-nitroarginine methyl ester (L-NAME), a NOS inhibitor, on development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in F344 male rats were investigated. Six-week-old male F344 rats were fed diets containing 0 or 100 ppm L-NAME, and given s.c. injections of AOM at 15 mg/kg body wt, once a week for 2 weeks. At 17 weeks of age, all animals were sacrificed and their colons were evaluated for numbers of ACF. Feeding of 100 ppm L-NAME inhibited the development of ACF in different sizes by 24-39%, those containing four or more crypts being most markedly affected. Assessment of silver-stained nucleolar organizer regions protein (AgNORs)/nucleus further revealed a 44% reduction by administration of L-NAME. These results suggest that the NOS inhibitor, L-NAME, may be an effective chemopreventive agent against colon carcinogenesis due to depression of cell proliferation.

  7. Chromoendoscopy with a Standard-Resolution Colonoscope for Evaluation of Rectal Aberrant Crypt Foci.

    Directory of Open Access Journals (Sweden)

    Marek Kowalczyk

    Full Text Available Colorectal cancer (CRC is the second most common cause of death worldwide. According to the theory by Vogelstein, colorectal carcinogenesis involves a series of successive changes in the normal colonic mucosa, starting with excessive proliferation and focal disorders of intestinal crypts, followed by adenoma and its subsequent malignant transformation. The first identifiable changes in CRC carcinogenesis are aberrant crypt foci (ACF. ACF are invisible during routine colonoscopy yet are well identifiable in chromoendoscopy using methylene blue or indigo carmine. High-resolution colonoscopes are used for assessment of ACF. The aim of the present study was to evaluate the usefulness of standard-resolution colonoscopy for identification of rectal ACF. The following parameters were evaluated: duration of chromoendoscopy of a given rectal segment, type of ACF, sensitivity and specificity of endoscopy combined with histopathological evaluation. The mean duration of colonoscopy and chromoendoscopy was 26.8 min. In the study population, typical ACF were found in 73 patients (p = 0.489, hyperplastic ACF in 49 (p = 0.328, and dysplastic ACF in 16 patients (p = 0.107. Mixed ACF were observed in 11 individuals (p = 0.073. The sensitivity of the method was found to be 0.96 whereas its specificity 0.99. Identification of rectal ACF using standard-resolution colonoscopy combined with rectal mucosa staining with 0.25% methylene blue is characterised by high sensitivity and specificity.

  8. Dietary cholesterol inhibits the development of aberrant crypt foci in the colon.

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    el-Sohemy, A; Kendall, C W; Rao, A V; Archer, M C; Bruce, W R

    1996-01-01

    We evaluated the effect of dietary cholesterol and oxidized cholesterol on the promotion of aberrant crypt foci (ACF), which are putative precancerous lesions in the colon. Sixty female C57BL/6J mice were given four weekly injections (ip) of azoxymethane (AOM) then fed either a control AIN-76 diet or the control diet supplemented with 0.3% cholesterol or 0.3% oxidized cholesterol for 100 days. The oxidized cholesterol was prepared by heating cholesterol at 110 degrees C for 48 hours. Gas chromatographic analysis of the oxidized cholesterol showed that 96% of the cholesterol was unchanged and less than 2% of the cholesterol was oxidized. The remaining 2% impurities were unidentified and present in both the cholesterol and heated cholesterol. The number of ACF in the group fed cholesterol was significantly lower than the control group (7.9 +/- 1.0 vs. 12.5 +/- 1.2, p < 0.01). The number of ACF in the group fed oxidized cholesterol (10.1 +/- 1.1) was not different from the control or cholesterol groups. The size of the ACF (no. of crypts per focus) did not differ between the three dietary groups. Serum low-density lipoprotein (LDL) cholesterol was greater in the cholesterol-fed group than the control group (40.5 +/- 4.6 vs. 24.3 +/- 3.6 mg/dl, p < 0.05). LDL cholesterol from the animals fed oxidized cholesterol (37.7 +/- 4.7 mg/dl) was not different from the control or cholesterol-fed animals. Total and high-density lipoprotein (HDL) cholesterol did not differ between the groups. The results show that dietary cholesterol significantly inhibits the promotion of ACF in the colon. The elevated LDL cholesterol may inhibit de novo cholesterol synthesis in the preneoplastic colonic epithelial cells, thereby inhibiting DNA synthesis and cell proliferation.

  9. Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings.

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    Yang, Kai; Fard, Sara; Furrer, Rudolf; Archer, Michael C; Bruce, W Robert; Lip, HoYin; Mehta, Rhea; O'Brien, Peter J; Giacca, Adria; Ward, Wendy E; Femia, A Pietro; Caderni, Giovanna; Medline, Alan; Banks, Kate

    2016-01-01

    Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.

  10. Epidemiology of Colonic Aberrant Crypt Foci: Review and Analysis of Existing Studies

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    Stevens, Richard G.; Swede, Helen; Rosenberg, Daniel W.

    2007-01-01

    Since first described in a rodent model in 1987, aberrant crypt foci (ACF) in the colon have been shown to exhibit many of the molecular features of the more advanced colonic neoplasms including cancer. Therefore, they may be early lesions with potential for progression, and be valuable biomarkers for reduction of risk of colorectal cancer (CRC). For this review, we searched PubMed, and reference lists of recent publications, for studies which reported on associations of features of ACF in humans, such as number or size, with subject characteristics, such as age or family history of CRC. Over 150 papers have reported on ACF in humans. However, the vast majority of these publications are concerned with molecular and morphological features of biopsied lesions, and not their epidemiology. None of the epidemiological studies were of optimum design, primarily due to their absence of a well-defined subject sampling frame or method. Given their ‘first-generation’ nature, consistent findings were of increased ACF number with age and with synchronous advanced colonic neoplasia. One study reported a higher mean number of ACF in subjects with a family history of CRC than in those without. The strongest evidence on the ability of ACF to predict a diagnosis of CRC will be from prospective studies with baseline ACF assessment in a large sample of disease-free persons (many thousands) who are followed carefully for many years. In the interim, because ACF are asymptomatic, well-designed cross-sectional studies are feasible and will yield valuable information on the relation of ACF to the known risk factors for CRC. This information can then be used to improve the design of prospective studies, and of clinical intervention trials that use ACF as an intermediate endpoint. PMID:17182176

  11. Dietary milk fat globule membrane reduces the incidence of aberrant crypt foci in Fischer-344 rats.

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    Snow, Dallin R; Jimenez-Flores, Rafael; Ward, Robert E; Cambell, Jesse; Young, Michael J; Nemere, Ilka; Hintze, Korry J

    2010-02-24

    Milk fat globule membrane (MFGM) is a biopolymer composed primarily of membrane proteins and lipids that surround the fat globules in milk. Although it is considered to have potential as a bioactive ingredient, few feeding studies have been conducted to measure its potential benefits. The aim of this investigation was to determine if dietary MFGM confers protection against colon carcinogenesis compared to diets containing corn oil (CO) or anhydrous milk fat (AMF). Male, weanling Fischer-344 rats were randomly assigned to one of three dietary treatments that differed only in the fat source: (1) AIN-76A diet, corn oil; (2) AIN-76A diet, AMF; and (3) AIN-76A diet, 50% MFGM, 50% AMF. Each diet contained 50 g/kg diet of fat. With the exception of the fat source, diets were formulated to be identical in macro and micro nutrient content. Animals were injected with 1,2-dimethylhydrazine once per week at weeks 3 and 4, and fed experimental diets for a total of 13 weeks. Over the course of the study dietary treatment did not affect food consumption, weight gain or body composition. After 13 weeks animals were sacrificed, colons were removed and aberrant crypt foci (ACF) were counted by microscopy. Rats fed the MFGM diet (n = 16) had significantly fewer ACF (20.9 +/- 5.7) compared to rats fed corn oil (n = 17) or AMF (n = 16) diets (31.3 +/- 9.5 and 29.8 +/- 11.4 respectively; P colonic mucosa did not reveal differential expression of candidate colon cancer genes, and the sphingolipid profile of the colonic mucosa was not affected by diet. While there were notable and significant differences in plasma and red blood cell lipids, there was no relationship to the cancer protection. These results support previous findings that dietary sphingolipids are protective against colon carcinogenesis yet extend this finding to MFGM, a milk fat fraction available as a food ingredient.

  12. Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats.

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    Boateng, J; Verghese, M; Shackelford, L; Walker, L T; Khatiwada, J; Ogutu, S; Williams, D S; Jones, J; Guyton, M; Asiamah, D; Henderson, F; Grant, L; DeBruce, M; Johnson, A; Washington, S; Chawan, C B

    2007-05-01

    Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF.

  13. Influence of Different Diets on Development of DMH-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

    DEFF Research Database (Denmark)

    Kristiansen, E.; Thorup, I.; Meyer, Otto A.

    1995-01-01

    The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACI;). Male Wistar rats were initiated with oral noses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once....... The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20, and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically...... significant increase (p less than or equal to 0.05) in the total number of ACF and number of small and medium ACF. Adding lard to the standard diet did not cause an increase in ACF, bur if the dietary fiber was added to the high-fat diet, a statistically significant reduction (p less than or equal to 0...

  14. Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Heemskerk, S.; Berg, van den J.H.J.; Alink, G.M.

    2003-01-01

    Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of

  15. Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer.

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    Compher, C W; Frankel, W L; Tazelaar, J; Lawson, J A; McKinney, S; Segall, S; Kinosian, B P; Williams, N N; Rombeau, J L

    1999-01-01

    Dietary wheat bran protects against colon cancer, but the mechanism(s) of this effect is not known. Butyrate, produced by colonic bacterial fermentation of dietary polysaccharides, such as wheat bran, induces apoptosis and decreases proliferation in colon cancer cell lines. Whether similar effects occur in vivo is not well defined. We hypothesized that wheat bran's antineoplastic effects in vivo may be mediated in part by butyrate's modulation of apoptosis and proliferation. Male F344 rats were fed wheat bran-supplemented or an isocaloric, isonitrogenous fiber-free diet. Rats were treated with one dose of the carcinogen azoxymethane or vehicle with sacrifice after 5 days (tumor initiation); or two doses (days O and 7) with sacrifice after 56 days (tumor promotion). Study variables included fecal butyrate levels and the intermediate biomarkers of colon carcinogenesis, aberrant crypt foci (ACF), and changes in crypt cell proliferation and apoptosis. During tumor initiation, wheat bran produced greater apoptosis (p = .01), a trend toward less proliferation, and preserved the normal zone of proliferation (p = .01). At tumor promotion, wheat bran decreased the number of ACF (proximal colon, p = .005; distal colon, p = .047) and maintained the normal proliferative zone. The fiber-free diet shifted the zone of proliferation into the premalignant pattern in both studies. Wheat bran produced significantly higher fecal butyrate (p = .01; .004, .00001) levels than the fiber-free diet throughout the tumor promotion study. Wheat bran increased apoptosis and controlled proliferation during tumor initiation and resulted in decreased ACF. Wheat bran's antineoplastic effects occurred early after carcinogen exposure, and were associated with increased fecal butyrate levels.

  16. Antitumor activity of the β-glucan paramylon from Euglena against preneoplastic colonic aberrant crypt foci in mice.

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    Watanabe, Toshiaki; Shimada, Ryoko; Matsuyama, Ai; Yuasa, Masahiro; Sawamura, Hiromi; Yoshida, Eriko; Suzuki, Kengo

    2013-11-01

    In the present study, the effects of β-glucans isolated from Euglena on the formation of preneoplastic aberrant crypt foci (ACF) in the colon were examined in mice. Mice were fed a semi-purified AIN-93M diet containing cellulose or the same diet but with the cellulose replaced with β-glucans in the form of Euglena, paramylon, or amorphous paramylon, for 11 weeks. After consuming these dietary supplements for 8 days, half of the mice were intraperitoneally administered 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) body weight every week for 6 weeks. Among the DMH-treated groups, the paramylon- and amorphous paramylon-fed mice displayed a significantly lower number of ACF than the control group. Also, the liver weight of the paramylon group was markedly decreased compared with those of the control and Euglena groups, whereas the cecal content weight and fecal volume of the paramylon group were significantly increased. As for the levels of organic acids in the cecal contents, the paramylon group displayed significantly increased lactic acid levels compared with the control and Euglena groups. From these findings, although the mechanism of the ACF-inhibiting effects of paramylon remains unclear, it is considered that β-glucans, such as paramylon and its isomer amorphous paramylon, have preventive effects against colon cancer and are more effective against the condition than Euglena.

  17. Initiation and promotion of colonic aberrant crypt foci in rats by 5-hydroxymethyl-2-furaldehyde in thermolyzed sucrose.

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    Zhang, X M; Chan, C C; Stamp, D; Minkin, S; Archer, M C; Bruce, W R

    1993-04-01

    We have previously shown that thermolyzed sucrose in the diet promotes the growth of aberrant crypt foci (ACF) in the rat. HPLC analysis of the light caramel colored product showed that it contained 1% 5-hydroxymethyl-2-furaldehyde (HMF), confirmed by mass and NMR spectroscopy. To determine whether HMF was responsible for the promotion of ACF by thermolyzed sucrose, 45 F344 female rats were initiated with the colon carcinogen azoxymethane (AOM), and a week later were randomized to four groups receiving AIN-76 diets containing untreated sucrose, 20% thermolyzed sucrose, 20% butanol extracted thermolyzed sucrose (HMF free) or 1% HMF. Thermolyzed sucrose in the diet led to larger ACF as previously observed. Thermolyzed sucrose extracted to remove HMF, did not affect ACF size, but 1% HMF added to the diet led to a larger ACF both with relation to average size and number of ACF of larger sizes (P < 0.05). To determine whether HMF had initiating effects, 172 female F344 rats were given water, HMF (at doses to 300 mg/kg) or AOM (5 mg/kg) by gavage twice and the total number of ACF was scored 30 days later. The results demonstrated that HMF induces ACF in a dose-dependent manner (P < 0.02), though the effect was much weaker than that of AOM. We conclude that sugar heated under household cooking conditions may act as both an initiator and a promoter of colon cancer because of the presence of HMF.

  18. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats

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    A.P.B. Moreira

    2009-12-01

    Full Text Available We determined the effect of fish oil (FO ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethylhydrazine (DMH at 3-day intervals and were fed a diet containing 18% by weight FO (N = 10 or soybean oil (SO, N = 10 for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (± SEM number of aberrant crypt foci compared to SO (113.55 ± 6.97 vs 214.60 ± 18.61; P 0.05. In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.

  19. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats.

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    Moreira, A P B; Sabarense, C M; Dias, C M G C; Lunz, W; Natali, A J; Glória, M B A; Peluzio, M C G

    2009-12-01

    We determined the effect of fish oil (FO) ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethylhydrazine (DMH) at 3-day intervals and were fed a diet containing 18% by weight FO (N = 10) or soybean oil (SO, N = 10) for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (+/- SEM) number of aberrant crypt foci compared to SO (113.55 +/- 6.97 vs 214.60 +/- 18.61; P colon was affected by diet (P 0.05). In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.

  20. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

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    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

  1. Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

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    Rodrigues M.A.M.

    2002-01-01

    Full Text Available Aberrant crypt foci (ACF in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks and medium-term (30 weeks assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks assay.

  2. Influence of a Dietary Fiber on Development of Dimethylhydrazine-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

    DEFF Research Database (Denmark)

    Thorup, I.; Meyer, Otto A.; Kristiansen, E.

    1994-01-01

    Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses...... between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small A CF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process...... of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 weeks were used as initiator. The rats were fed different levels of the fiber in a preinitiation period, during initiation, or in a postinitiation period. In general, the results showed a statistically significant inverse relation...

  3. DNA damage and aberrant crypt foci as putative biomarkers to evaluate the chemopreventive effect of annatto (Bixa orellana L.) in rat colon carcinogenesis.

    Science.gov (United States)

    Agner, Aniele R; Bazo, Ana P; Ribeiro, Lúcia R; Salvadori, Daisy M F

    2005-04-04

    Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of such potential chemopreventive agents. Colon cancer is one of the highest incidence rates throughout the world and some evidences have indicated carotenoids as possible agents that decrease the risk of colorectal cancer. In the present study, we evaluate the activity of annatto (Bixa orellana L.), a natural food colorant rich in carotenoid, on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) in rat colon. Further, we investigate, the effect of annatto on DMH-induced DNA damage, by the comet assay. Male Wistar rats were given s.c. injections of DMH (40 mg/kg body wt.) twice a week for 2 weeks to induce ACF. They also received experimental diets containing annatto at 20, 200 or 1000 ppm for five 5 weeks before (pre-treatment), or 10 weeks after (post-treatment) DMH treatment. In both protocols the rats were sacrificed on week 15th. For the comet assay, the animals were fed with the same experimental diets for 2 weeks. Four hours before the sacrifice, the animals received an s.c. injection of DMH (40 mg/kg body wt.). Under such conditions, dietary administration of 1000 ppm annatto neither induce DNA damage in blood and colon cells nor aberrant crypt foci in rat distal colon. Conversely, annatto was successful in inhibiting the number of crypts/colon (animal), but not in the incidence of DMH-induced ACF, mainly when administered after DMH. However, no antigenotoxic effect was observed in colon cells. These findings suggest possible chemopreventive effects of annatto through their modulation of the cryptal cell proliferation but not at the initiation stage of colon carcinogenesis.

  4. IQ (2-amino-3-methylimidazo[4,5-f]quinoline)- induced aberrant crypt foci and colorectal tumour development in rats fed two different carbohydrate diets

    DEFF Research Database (Denmark)

    Mølck, A.M.; Meyer, Otto A.; Kristiansen, E.

    2001-01-01

    In most aberrant crypt foci (ACF) and colorectal tumour studies, chemical carcinogens not normally found in food have been used as initiators. In the present study the food-related compound, IQ (2-amino-3-methylimidazo[4,5-f]quinoline), has been used. A diet high in refined carbohydrates has been...... on the development of IQ-induced ACF over time and (2) possible correlation between early and late ACF and/or colorectal tumour development. The study showed that a feeding regimen with continuous doses of 0.03% IQ in the diet for 14 weeks, followed by 32 weeks without IQ was able to induce tumours in the rat colon...

  5. The combination of 1α, 25(OH)2 – Vitamin D3, calcium and acetylsalicyclic acid affects azoxymethane-induced aberrant crypt foci and colorectal tumours in rats

    DEFF Research Database (Denmark)

    Mølck, Anne-Marie; Poulsen, Morten; Meyer, Otto A.

    2002-01-01

    Effects of 1alpha,25(OH)(2)-vitamin D(3) and acetylsalicylic acid at various dietary levels of calcium (CaCO(3)) on development of aberrant crypt foci (ACF) and tumours in colon were examined in groups of 16 male F344 rats initiated with azoxymethane and observed for 16 weeks. Calcium was the most...... potent modulator of ACF development. The total number of ACF increased with low calcium and decreased with high calcium. The number of large ACF decreased with any addition of calcium, acetylsalicylic acid and 1alpha,25(OH)(2)-vitamin D(3). High levels of calcium alone or in combination with 1alpha,25(OH......)(2)-vitamin D(3) increased the incidence of tumour-bearing animals. 1alpha,25(OH)(2)-vitamin D(3) and acetylsalicylic acid at 5,000 ppm calcium increased the incidence as well....

  6. The influence of simple sugars and starch given during pre- or post-initiation on aberrant crypt foci in rat colon

    DEFF Research Database (Denmark)

    Poulsen, Morten; Mølck, Anne-Marie; Thorup, Inger

    2001-01-01

    The aim of the present study was to investigate the enhancing effect of dietary sugar on the development of aberrant crypt foci (ACF) in male F344 rats initiated with azoxymethane (AOM). The potential role of sugar as either a co-initiator or a promoter was investigated by giving diets high...... on the specific mechanisms involved in the suggested effect of sucrose and dextrin on ACF development. The number of large sized and the total number of ACF were significantly increased by feeding sucrose and dextrin in the post-initiation period. No positive association between colonic cell proliferation and ACF...... was seen. The level of oxidative stress in the cytosol from the proximal colon and colonic glutathione transferase and quinone reductase was not affected by the sugar treatments. The overall results from this study show that sucrose and dextrin enhance the number of preneoplastic lesions in AOM...

  7. An n-3 PUFA-rich microalgal oil diet protects to a similar extent as a fish oil-rich diet against AOM-induced colonic aberrant crypt foci in male F344 rats

    NARCIS (Netherlands)

    Beelen, van V.A.; Spenkelink, A.; Mooibroek, H.; Sijtsma, L.; Bosch, H.J.; Rietjens, I.M.C.M.; Alink, G.M.

    2009-01-01

    The chemopreventive effects of high fat microalgal oil diet on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male Fischer 344 rats following 8 weeks of dietary treatment. These effects were compared to the effects of high fat fish oil and high fat corn oil diets to

  8. Influence of a dietary fiber on development of dimethylhydrazine-induced aberrant crypt foci and colon tumor incidence in Wistar rats.

    Science.gov (United States)

    Thorup, I; Meyer, O; Kristiansen, E

    1994-01-01

    Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 weeks were used as initiator. The rats were fed different levels of the fiber in a preinitiation period, during initiation, or in a postinitiation period. In general, the results showed a statistically significant inverse relation between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small ACF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process. The lack of correlation between the outcome of ACF and tumors could be related to the observation that statistically significant differences between groups were seen only in the total number of ACF and number of small ACF. The hypothesis that ACF are preneoplastic lesions needs to be supported by further experimental data. The present state of knowledge could indicate that ACF represent true preneoplastic lesions progressing into colon tumors or that ACF and colon tumors represent two parallel independent events as a consequence of the cancer initiation (i.e., the ACF not being preneoplastic lesions per se).

  9. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Lokesh Kumar Booupathy

    2016-01-01

    Full Text Available Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF. Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

  10. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer

    Directory of Open Access Journals (Sweden)

    W. Lunz

    2008-11-01

    Full Text Available We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old were given 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5, at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11, 2% body weight (EG2, N = 11, and 4% body weight of load (EG3, N = 10, 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10. At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05. Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%. Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³. Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g. Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

  11. Synbiotic preparation with Lactic acid bacteria and inulin as a functional food: In vivo evaluation of microbial activities, and preneoplastic aberrant crypt foci

    Directory of Open Access Journals (Sweden)

    Chaiyavat CHAIYASUT

    Full Text Available Abstract Host microbiome and metabolome are associated with the incidence of colorectal cancer (CC, one of the major health problems in developed countries. The pro and prebiotic supplementation helps to improve the host health. Inulin is one such prebiotic used for the enhancement of naïve probiotic bacterial population. This paper explains the impact of inulin (PRE extracted from Jerusalem artichoke (JA, Lactobacillus plantarum HII11 (PRO, and synbiotic (SYN; inulin + L. plantarum HII11 preparation on Azoxymethane mediated CC induced rat model with respect to changes in microbial load, microbial enzymes, and preneoplastic aberrant crypt foci. The results suggested that the PRE and SYN supplementation effectively reduced the selected pathogenic bacteria (Salmonella spp., and Escherichia coli, microbial enzymes and increased the probiotic load. The intervention of SYN significantly reduced the colonic ACF in CC model. The study results revealed that the supplementation of SYN diet (inulin and L. plantarum HII11 protects the AOM-mediated colon cancer induced host.

  12. Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.

    Science.gov (United States)

    Qamar, Tahir Rasool; Syed, Fatima; Nasir, Muhammad; Rehman, Habib; Zahid, Muhammad Nauman; Liu, Rui Hai; Iqbal, Sanaullah

    2016-08-01

    The selectivity and beneficial effects of prebiotics are mainly dependent on composition and glycosidic linkage among monosaccharide units. This is the first study to use prebiotic galacto-oligosaccharides (GOS) that contains β-1,6 and β-1,3 glycosidic linkages and the novel combination of GOS and inulin in cancer prevention. The objective of the present study is to explore the role of novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114 mg), were given to DMH-treated animals for 16 weeks. Our data reveal the significant preventive effect of the GOS and inulin combination against the development of CRC. It was observed that inhibition of ACF formation (55.8%) was significantly (p ≤ 0.05) higher using the GOS and inulin combination than GOS (41.4%) and inulin (51.2%) treatments alone. This combination also rendered better results on short-chain fatty acids (SCFA) and bacterial enzymatic activities. Dose-dependent effects of prebiotic treatments were also observed on cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that novel combination of GOS and inulin exhibited stronger preventive activity than their individual treatments alone, and can be a promising strategy for CRC chemoprevention.

  13. Effect of celecoxib and cisplatin combination on apoptosis and cell proliferation in a mouse model of chemically-induced colonic aberrant crypt foci

    Directory of Open Access Journals (Sweden)

    Soha S. Essawy

    2017-12-01

    Full Text Available The use of cisplatin for the treatment of cancer is accompanied by dose-dependent adverse effects. In colorectal cancer, there is upregulation of cyclooxygenase-2 (COX-2 expression increases prostaglandin E2 (PGE2 which in turn depresses apoptosis and potentiates invasion, angiogenesis, cell-proliferation and metastasis. This study investigates a possible synergistic function for celecoxib in cisplatin-based chemotherapy against chemically-induced colon carcinogenesis in mice. Mice received fifteen injections of 1,2-dimethylhydrazine dihydrochloride (DMH; 20 mg/kg/week, s.c. to induce colon carcinogenesis and the normal control group received equal volumes of normal saline. Mice were randomly divided into five groups, (I normal control group, (II DMH control group (III DMH + cisplatin (4 mg/kg/week, i.p. group, (IV DMH + celecoxib (10 mg/kg/day by gavage group and (V DMH + cisplatin + celecoxib group. Drugs were administered starting from week eleven until the end of the experiment (week 15. Colon specimens were used to evaluate histological grades, examine intratumoral expression of Bcl2, BAX and caspase-3 and the number of proliferating nuclei. The combination of cisplatin and celecoxib was effective against malignant transformation in mice with DMH-induced colonic aberrant crypt foci (ACF. The combination group showed improvement in histological grading, the highest caspase-3 expression and the lowest Bcl2/BAX ratio and reduction by approximately 50% of immunoreactivity for proliferating cell nuclear antigen (PCNA compared to DMH control group. Addition of celecoxib to cisplatin regimen promotes apoptosis, suppresses tumor proliferation and augments the antitumor effect of cisplatin chemotherapy in the mouse model of DMH-induced ACF. Keywords: BAX, BCl2, Caspase-3, Celecoxib, Cisplatin, 1,2-Dimethylhydrazine, PCNA, Colonic ACF

  14. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Elnaz Saki

    2017-01-01

    Full Text Available Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age were randomly divided into 5 groups which were (G1 induced with azoxymethane (AOM and not given GRR (positive control, (G2 induced with AOM and given 2000 mg/kg GRR, (G3 induced with AOM and given 1000 mg/kg GRR, (G4 induced with AOM and given 500 mg/kg GRR, and (G5 not induced with AOM and not given GRR crude extract (negative control. To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

  15. Effect of dietary fibre of barley variety 'Rihane' on azoxymethane-induced aberrant crypt foci development and on colonic microbiota diversity in rats.

    Science.gov (United States)

    Lahouar, Lamia; Pochart, Philippe; Salem, Hichem Ben; El Felah, Mouledi; Mokni, Moncef; Magne, Fabien; Mangin, Irène; Suau, Antonia; Pereira, Ester; Hammami, Mohamed; Achour, Lotfi

    2012-12-14

    Many epidemiological and experimental studies have suggested an important role for dietary fibre (DF) of cereals in the prevention of colon cancer. The objective of the present study was to explain the effects of the DF of barley Rihane (BR) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and colonic bacterial diversity in rats. Following an acclimatisation period, rats were divided into four groups and fed a control (C) diet or experimental diet containing 30 % of BR. DF content in the experimental diet was twice that of the C diet (total DF was 8·69 % in the C diet and 15·24 % in the BR diet). At 7 and 8 weeks of age, rats received two successive subcutaneous injections of AOM at 20 mg/kg body weight. At 12 weeks after the first injection, ten animals from each group were killed. The BR diet decreased colonic pH (P colonic microbiota species between the different groups. In addition, we showed inter-individual variability within the same group. This similarity was affected by BR and AOM. The present results show that bifidobacteria numbers were lower in rats fed the BR diet compared with those fed the C diet. However, the number of enterobacteria in colonic content was increased (P < 0·05) in the BR group compared with the C group. The results from the present study show that the DF of BR reduced the incidence of AOM-induced ACF and increased microbiota biodiversity.

  16. Chemopreventive effect of raw and cooked lentils (Lens culinaris L) and soybeans (Glycine max) against azoxymethane-induced aberrant crypt foci.

    Science.gov (United States)

    Faris, Mo'ez Al-Islam E; Takruri, Hamed R; Shomaf, Maha S; Bustanji, Yasser K

    2009-05-01

    Although lentils (Lens culinaris L) contain several bioactive compounds that have been linked to the prevention of cancer, the in vivo chemopreventive ability of lentils against chemically induced colorectal cancer has not been examined. Our present study examined the hypothesis that lentils could suppress the early carcinogenesis in vivo by virtue of their bioactive micro- and macroconstituents and that culinary thermal treatment could affect their chemopreventive potential. To accomplish this goal, we used raw whole lentils (RWL), raw split lentils (RSL), cooked whole lentils (CWL), and cooked split lentils (CSL). Raw soybeans (RSB; Glycine max) were used for the purpose of comparison with a well-studied chemopreventive agent. Sixty weanling Fischer 344 male rats, 4 to 5 weeks of age, were randomly assigned to 6 groups (10 rats/group): the control group (C) received AIN-93G diet, and treatment leguminous groups of RWL, CWL, RSL, CSL, and RSB received the treatment diets containing AIN-93G+5% of the above-mentioned legumes. After acclimatization for 1 week (at 5th to 6th week of age), all animals were put on the control and treatment diets separately for 5 weeks (from 6th to 11th week of age). At the end of the 5th week of feeding (end of 11th week of age), all rats received 2 subcutaneous injections of azoxymethane carcinogen at 15 mg/kg rat body weight per dose once a week for 2 consecutive weeks. After 17 weeks of the last azoxymethane injection (from 12th to 29th week of age), all rats were euthanized. Chemopreventive ability was assessed using colonic aberrant crypt foci and activity of hepatic glutathione-S-transferases. Significant reductions (P lentils might be protective against colon carcinogenesis and that hydrothermal treatment resulted in an improvement in the chemopreventive potential for the whole lentils.

  17. Dietary aloe vera gel powder and extract inhibit azoxymethane- induced colorectal aberrant crypt foci in mice fed a high- fat diet.

    Science.gov (United States)

    Chihara, Takeshi; Shimpo, Kan; Kaneko, Takaaki; Beppu, Hidehiko; Higashiguchi, Takashi; Sonoda, Shigeru; Tanaka, Miyuki; Yamada, Muneo; Abe, Fumiaki

    2015-01-01

    Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

  18. Inhibition of Formation of Azoxymethane-induced Colonic Aberrant Crypt Foci in Rats by Edible Green AlgaeCapsosiphon fulvescensand Brown AlgaeHizikia fusiforme.

    Science.gov (United States)

    Son, Young-Sook; Ullah, H M Arif; Elfadl, Ahmed K; Ghim, Soong-Gu; Chung, Myung-Jin; Kim, Yong Deuk; Lee, Eun-Joo; Kang, Kyung-Ku; Jeong, Kyu-Shik

    2018-01-01

    Capsosiphon fulvescens (green seaweed) and Hizikia fusiforme (brown seaweed) are marine algae consumed as food supplements, especially in Japan, China and Korea, and are considered traditional medicinal tonics for certain ailments. The aim of this study was to investigate the possible inhibitory effects of dietary C. fulvescens and H. fusiforme on azoxymethane (AOM)-induced colorectal cancer (CRC) in rats. F344 male rats (5 weeks, 150 g) were divided into six groups as follows. Group 1: Injected with normal saline solution and fed control diet (untreated control). Group 2: Injected with AOM and fed control diet (treated control). Group 3: Injected with AOM and fed 1% C. fulvescens diet. Group 4: Injected with AOM and fed 2% C. fulvescens diet. Group 5: Injected with AOM and fed 2% H. fusiforme diet. Group 6: Injected with AOM and fed 6% H. fusiforme diet. Test animals received subcutaneous injections of AOM (15 mg/1 ml/kg body weight) once a week for 2 weeks to induce aberrant crypt foci (ACF) in treated control and experimental groups. We evaluated the effects of dietary C. fulvescens and H. fusiforme at two different dose levels: 1 and 2% C. fulvescens, and 2 and 6% H. fusiforme, on colonic carcinogenesis by AOM in rats. Our results suggest that body weights were not significantly different amongst groups. We found that feeding C. fulvescens and H. fusiforme with a control diet significantly (p<0.05) inhibited the development of ACF in experimental groups. C. fulvescens and H. fusiforme in food also significantly (p<0.05) reduced the proliferating cell nuclear antigen labeling index in the colonic tissues of experimental groups. These results demonstrate the chemopreventive potential of C. fulvescens and H. fusiforme against CRC in an AOM-induced rats. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    Science.gov (United States)

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  20. Protective effect of lactofermented red beetroot juice against aberrant crypt foci formation, genotoxicity of fecal water and oxidative stress induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in rats model.

    Science.gov (United States)

    Klewicka, Elżbieta; Nowak, Adriana; Zduńczyk, Zenon; Juśkiewicz, Jerzy; Cukrowska, Bożena

    2012-11-01

    The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was used as carcinogen, which was administrated intragastrically at a dose of 10 μg/day, every day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco-2 cell line, evaluated by MTT test and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization. Oxidative stress in rats was expressed by measuring serum antioxidant status and the level of malondialdehyde in the kidneys and liver. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and PhIP treatment, and basal diet supplemented with FBJ and PhIP treatment. FBJ significantly reduced the number of ACF in PhIP-treated rats (from 59 ± 18 to 26 ± 4). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 52 ± 18 to 18 ± 4. Fecal water obtained from rats fed with a PhIP-containing diet induced pronounced cytotoxic and genotoxic effects in Caco-2 cells, but FBJ supplementation of the diet abolished these effects. In groups fed dietary PhP and FBJ the latter was found to increase the antioxidant status of serum from 40% to 66% depending on the fraction. Reduced concentration of malondialdehyde was found only in the kidneys of rats fed with PhIP and FBJ. FBJ present in the diet of rats causes a reduction of MDA in the kidneys from 118.7 nmol/g tissue to 100 nmol/g tissue. The presence of FBJ in the diet of rats significantly increased the count of bacteria, including Lactobacillus/Enterococcus and Bacteroides-Prevotella group adhered to colonic epithelium. In conclusion

  1. An n-3 PUFA-rich microalgal oil diet protects to a similar extent as a fish oil-rich diet against AOM-induced colonic aberrant crypt foci in F344 rats.

    Science.gov (United States)

    van Beelen, Vincent A; Spenkelink, Bert; Mooibroek, Hans; Sijtsma, Lolke; Bosch, Dirk; Rietjens, Ivonne M C M; Alink, Gerrit M

    2009-02-01

    The chemopreventive effects of high fat microalgal oil diet on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male Fischer 344 rats following 8 weeks of dietary treatment. These effects were compared to the effects of high fat fish oil and high fat corn oil diets to determine whether microalgal oil is a good alternative for fish oil regarding protection against colorectal cancer. Despite the difference in fatty acid composition and total amount of n-3 polyunsaturated fatty acids (PUFAs) between microalgal oil and fish oil, both these oils gave the same 50% reduction of AOM-induced ACF when compared to corn oil. To determine whether oxidative stress could play a role in the chemoprevention of colorectal cancer by n-3 PUFAs, feces and caecal content were examined using the TBA assay. The results showed that lipid peroxidation does occur in the gastrointestinal tract. As several lipid peroxidation products of n-3 PUFAs can induce phase II detoxifying enzymes by an EpRE-mediated pathway, the in vivo results suggest that this route may contribute to n-3 PUFA-mediated chemoprevention. All in all, n-3 PUFA-rich oil from microalgae is as good as fish oil regarding chemoprevention in the colon of the rat.

  2. The chemopotential effect of Annona muricata leaves against azoxymethane-induced colonic aberrant crypt foci in rats and the apoptotic effect of Acetogenin Annomuricin E in HT-29 cells: a bioassay-guided approach.

    Science.gov (United States)

    Zorofchian Moghadamtousi, Soheil; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Firoozinia, Mohammad; Ameen Abdulla, Mahmood; Abdul Kadir, Habsah

    2015-01-01

    Annona muricata has been used in folk medicine for the treatment of cancer and tumors. This study evaluated the chemopreventive properties of an ethyl acetate extract of A. muricata leaves (EEAML) on azoxymethane-induced colonic aberrant crypt foci (ACF) in rats. Moreover, the cytotoxic compound of EEAML (Annomuricin E) was isolated, and its apoptosis-inducing effect was investigated against HT-29 colon cancer cell line using a bioassay-guided approach. This experiment was performed on five groups of rats: negative control, cancer control, EEAML (250 mg/kg), EEAML (500 mg/kg) and positive control (5-fluorouracil). Methylene blue staining of colorectal specimens showed that application of EEAML at both doses significantly reduced the colonic ACF formation compared with the cancer control group. Immunohistochemistry analysis showed the down-regulation of PCNA and Bcl-2 proteins and the up-regulation of Bax protein after administration of EEAML compared with the cancer control group. In addition, an increase in the levels of enzymatic antioxidants and a decrease in the malondialdehyde level of the colon tissue homogenates were observed, suggesting the suppression of lipid peroxidation. Annomuricin E inhibited the growth of HT-29 cells with an IC50 value of 1.62 ± 0.24 μg/ml after 48 h. The cytotoxic effect of annomuricin E was further substantiated by G1 cell cycle arrest and early apoptosis induction in HT-29 cells. Annomuricin E triggered mitochondria-initiated events, including the dissipation of the mitochondrial membrane potential and the leakage of cytochrome c from the mitochondria. Prior to these events, annomuricin E activated caspase 3/7 and caspase 9. Upstream, annomuricin E induced a time-dependent upregulation of Bax and downregulation of Bcl-2 at the mRNA and protein levels. In conclusion, these findings substantiate the usage of A. muricata leaves in ethnomedicine against cancer and highlight annomuricin E as one of the contributing compounds in the

  3. The effects of dietary selenomethionine on polyamines and azoxymethane-induced aberrant crypts.

    Science.gov (United States)

    Baines, A T; Holubec, H; Basye, J L; Thorne, P; Bhattacharyya, A K; Spallholz, J; Shriver, B; Cui, H; Roe, D; Clark, L C; Earnest, D L; Nelson, M A

    2000-11-28

    We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.

  4. Knockout of the 15 kDa selenoprotein protects against chemically-induced aberrant crypt formation in mice.

    Directory of Open Access Journals (Sweden)

    Petra A Tsuji

    Full Text Available Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15 in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg. Sep15 knockout mice developed significantly (p<0.001 fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1 mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.

  5. Aberrant crypt formation accompanies an increase of opportunistic pathogens/bacteria in the inflammatory gut of C57BL/6 mice fed a high-fat diet

    Science.gov (United States)

    Obesity and high fat diet are risk factors for colon cancer, but the mechanism of this relationship remains to be determined. We tested the hypothesis that a high fat diet promotes the formation of aberrant crypt foci (ACF, preneoplastic lesions) in a manner associated with changes in hindgut bacter...

  6. Suggestive evidence for the induction of colonic aberrant crypts in mice fed sodium nitrite.

    Science.gov (United States)

    Zhou, Lin; Zahid, Muhammad; Anwar, Muhammad M; Pennington, Karen L; Cohen, Samuel M; Wisecarver, James L; Shostrom, Valerie; Mirvish, Sidney S

    2016-01-01

    A reported linkage between processed (nitrite-treated) meat products and the incidence of colon cancer could be due to sodium nitrite (NaNO2) itself or to N-nitroso compounds produced from the nitrite. Exposure to nitrite occurs due to residual nitrite in processed meat and to salivary nitrite arising by reduction of nitrate in vegetables and drinking water. Here we tested whether NaNO2 could induce colonic aberrant crypts (ABC) or ABC foci (ACF), which are putative precursors of colon cancer. We fed NaNO2 in drinking water for 20-25 wk to groups of 8-20 adult female mice. After sacrifice, ABC and ACF were counted in 2-cm distal colonic segments. In Experiment 1, no significant differences in ABC/ACF induction were seen between groups of 13-14 A/J mice fed 0, 0.5, or 1.0 g NaNO2/l drinking water. NaNO2 also did not affect fasting blood glucose levels. In Experiment 2, we fed 0, 1.0, 1.25, or 1.5 g NaNO2/l water to groups of 15 CF-1 mice. Five of the mice fed 1.5 g NaNO2/l showed ABC, whereas all other groups showed only 0-2 ABC/group, including 0 ABC for the group fed 1.25 g NaNO2/l. Overall statistical analysis indicated a dose-response p trends of 0.04. Pairwise comparison of ABC between groups fed 1.25 and 1.5 g NaNO2/l showed p 0.02 for both ABC and ACF, but a similar comparison between the untreated and 1.5 g/l groups showed no significant effects. In Experiment 3, hot dogs (18% of diet), which were fed to CF-1 mice previously treated with azoxymethane, inhibited ABC and ACF induction, but this effect was not significant (P = 0.10-0.12). In conclusion, these results support the view that NaNO2 may be a risk factor for colon carcinogenesis.

  7. Dietary Ziziphus jujuba Fruit Influence on Aberrant Crypt Formation and Blood Cells in Colitis-Associated Colorectal Cancer in Mice.

    Science.gov (United States)

    Periasamy, Srinivasan; Liu, Chung-Teng; Wu, Wang-Hung; Chien, Se-Ping; Liu, Ming-Yie

    2015-01-01

    Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary complaints. However, dietary effects with regard to chemoprevention of colon cancer have not been studied. The present study was performed to evaluate the protective effects of dietary ZJ against colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between were administered to induce colitis-associated colon cancer. ZJ fruit was supplemented into feed at levels of 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation and also decreased the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation may delay the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leukocytes, main regulators of cancer inflammation. Dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

  8. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  9. Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs.

    Science.gov (United States)

    Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

    2012-01-01

    Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5 mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17-34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5-6, with P dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon.

  10. Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs.

    OpenAIRE

    Davis, Michael E.; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L.; Gulizia, James M.; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E.; Mirvish, Sidney S

    2012-01-01

    International audience; Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5 mg azoxymethane (AOM)/kg. In Experiments 1 and 2, ...

  11. A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    McGinley John N

    2010-05-01

    Full Text Available Abstract The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF, a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity. Additional file 1 Click here for file

  12. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon.

    Science.gov (United States)

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-20

    Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.

  13. Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet

    Science.gov (United States)

    Background: The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat western diet, but the mechanism underlying this relationship remains to be determined. Objective: We tested the hypothesis that a high-fat diet promotes aberrant crypt (AC) format...

  14. The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

    Science.gov (United States)

    Winkelmann, Isabel; Diehl, Daniela; Oesterle, Doris; Daniel, Hannelore; Wenzel, Uwe

    2007-07-01

    Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism.

  15. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

    2011-01-01

    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

  16. Effect of diets fortified with tomatoes or onions with variable quercetin-glycoside content on azoxymethane-induced aberrant crypt foci in the colon of rats

    NARCIS (Netherlands)

    Femia, A.P.; Caderni, G.; Ianni, M.; Salvadori, M.; Schijlen, E.G.W.M.; Collins, G.; Bovy, A.G.; Dolara, P.

    2003-01-01

    Background: Onion and tomato are vegetables widely consumed by humans and epidemiological studies show an inverse association between vegetable consumption and colon cancer risk; however, the effect on colon cancer of diets containing high levels of vegetables like onion and tomato are not clear.

  17. Synbiotic preparation with Lactic acid bacteria and inulin as a functional food: In vivo evaluation of microbial activities, and preneoplastic aberrant crypt foci

    OpenAIRE

    Chaiyasut,Chaiyavat; Thanawat PATTANANANDECHA; Sirilun, Sasithorn; Suwannalert, Prasit; Sartjin PEERAJAN; Bhagavathi Sundaram SIVAMARUTHI

    2017-01-01

    Abstract Host microbiome and metabolome are associated with the incidence of colorectal cancer (CC), one of the major health problems in developed countries. The pro and prebiotic supplementation helps to improve the host health. Inulin is one such prebiotic used for the enhancement of naïve probiotic bacterial population. This paper explains the impact of inulin (PRE) extracted from Jerusalem artichoke (JA), Lactobacillus plantarum HII11 (PRO), and synbiotic (SYN; inulin + L. plantarum HII11...

  18. TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATS

    Science.gov (United States)

    Folate and folic acid are forms of the B vitamin that are involved in the synthesis, repair and functioning of DNA and are required for the production and maintenance of cells. Low levels of folate have been associated with several forms of cancer, including colon cancer. Aberran...

  19. Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats

    DEFF Research Database (Denmark)

    Poulsen, Morten; Molck, Anne-Marie; Jacobsen, Bodil Lund

    2002-01-01

    Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin...

  20. Crowns and Crypts

    Indian Academy of Sciences (India)

    thesis of stable complexes of all Group-! elements. Crypts form similar but much more stable complexes, also with the alkaline earths. The stabilization ofless familiar oxidation states of a large number of elements using crowns and crypts became an easy task. The basic and the oxidising properties of KOH and KMnO 4'.

  1. Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt formation in rat colonic mucosa Efeito de uma dieta hiperlipídica rica em ômegas 3, 6 e 9 na formação de criptas aberrantes em mucosa cólica de ratos

    Directory of Open Access Journals (Sweden)

    Idália Maria Brasil Burlamaqui

    2012-01-01

    Full Text Available PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF in colonic mucosa of Wistar rats treated with azoxymethane (AOM. METHODS: At eight weeks of life, the rats were assigned to four groups: Group I―standard diet (STD not treated with AOM; Group II―hypercaloric and hyperlipidic diet (FED, not treated with AOM; Group III―STD, treated with AOM; Group IV―FED, treated with AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9% saline solution (Group I and II or AOM at 15mg/Kg (Groups III and IV once a week for two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED promoted weight gain in Groups II and IV compared to Groups I and III, respectively. The groups did not differ with regard to the total number of ACF. The Chi-square test revealed no predominance of the presence of foci with OBJETIVO: Determinar se uma dieta hipercalórica, hiperlipídica, rica em ácidos graxos poliinsaturados (FED tem influência na formação de focos de cripta aberrante (FCA em mucosa cólica de ratos Wistar expostos ao azoximetano (AOM. MÉTODOS: Com oito semanas de vida, os ratos foram distribuídos em quatro grupos: Grupo I: Dieta padrão (SD sem AOM; Grupo II: FED, sem AOM; Grupo III: SD, com AOM; Grupo IV: FED com AOM. Com 16 semanas, os animais dos grupos I e II receberam injeções intraperitoneais de solução salina 0,9%, enquanto os dos grupos III e IV receberam AOM na dose de 15mg/Kg de peso, 1 vez por semana por duas semanas. Quinze semanas após, os animais foram mortos. RESULTADOS: FED promoveu aumento de peso nos grupos II e IV em relação aos grupos I e III. Não houve aumento significante no número total de FCA entre os grupos. Em relação à multiplicidade das criptas por FCA, o teste do qui-quadrado mostrou que não houve predominância da presença <4 criptas por foco. Contudo, focos ≥5 criptas

  2. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1996-01-01

    ,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis....... In the present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can...

  3. Using crypts as iris minutiae

    Science.gov (United States)

    Shen, Feng; Flynn, Patrick J.

    2013-05-01

    Iris recognition is one of the most reliable biometric technologies for identity recognition and verification, but it has not been used in a forensic context because the representation and matching of iris features are not straightforward for traditional iris recognition techniques. In this paper we concentrate on the iris crypt as a visible feature used to represent the characteristics of irises in a similar way to fingerprint minutiae. The matching of crypts is based on their appearances and locations. The number of matching crypt pairs found between two irises can be used for identity verification and the convenience of manual inspection makes iris crypts a potential candidate for forensic applications.

  4. Bodies Folded in Migrant Crypts

    DEFF Research Database (Denmark)

    Galis, Vasilis; Tzokas, Spyros; Tympas, Aristotle

    2016-01-01

    and human migrants generates a dis/abled subject. In this context, dis/ability may be a cause or consequence of migration, both in physical/material (the folding of bodies in the crypt) and cultural/semiotic terms, and may become a barrier to accessing protection, to entering and/or crossing a country......, and to performing mobility in general. Dis/ability and migration have not been associated in the literature. We adopt an analytical symmetry between humans and non-humans, in this case between bodies and crypts. By suggesting an infected, ambivalent, and hybrid approach to the human subject, the body...

  5. Bodies Folded in Migrant Crypts

    DEFF Research Database (Denmark)

    Galis, Vasilis; Tzokas, Spyros; Tympas, Aristotle

    2016-01-01

    This article considers media narratives that suggest that hiding in trucks, buses, and other vehicles to cross borders has, in fact, been a common practice in the context of migration to, and within, Europe. We aim to problematize how the tension between the materiality of bordering practices...... and human migrants generates a dis/abled subject. In this context, dis/ability may be a cause or consequence of migration, both in physical/material (the folding of bodies in the crypt) and cultural/semiotic terms, and may become a barrier to accessing protection, to entering and/or crossing a country......-crypt traveling border challenges the essentialist dichotomies between technology and biology, disability and impairment. The articles and reports upon which we rely were collected through extensive searches of databases/archives of online newspapers and news websites....

  6. Allyl sulfur compounds from garlic modulate aberrant crypt formation.

    OpenAIRE

    Ross, Sharon A.; Finley, John W.; Milner, John A.

    2006-01-01

    KEYWORDS - CLASSIFICATION: Adenoma;Animals;Anticarcinogenic Agents;chemically induced;Colonic Neoplasms;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Disease Models,Animal;Garlic;prevention & control;Plant Extracts;Precancerous Conditions;Research;Rodentia;Sulfinic Acids;therapeutic use. The health benefits of garlic, including inhibition of carcinogenesis, are supported by several epidemiologic and laboratory findings. Garlic's sulf...

  7. The APC Network Regulates the Removal of Mutated Cells from Colonic Crypts

    Directory of Open Access Journals (Sweden)

    Je-Hoon Song

    2014-04-01

    Full Text Available Self-renewal is essential for multicellular organisms but carries the risk of somatic mutations that can lead to cancer, which is particularly critical for rapidly renewing tissues in a highly mutagenic environment such as the intestinal epithelium. Using computational modeling and in vivo experimentation, we have analyzed how adenomatous polyposis coli (APC mutations and β-catenin aberrations affect the maintenance of mutant cells in colonic crypts. The increasing abundance of APC along the crypt axis forms a gradient of cellular adhesion that causes more proliferative cells to accelerate their movement toward the top of the crypt, where they are shed into the lumen. Thus, the normal crypt can efficiently eliminate β-catenin mutant cells, whereas APC mutations favor retention. Together, the molecular design of the APC/β-catenin signaling network integrates cell proliferation and migration dynamics to translate intracellular signal processing and protein gradients along the crypt into intercellular interactions and whole-crypt physiological or pathological behavior.

  8. Enzootic plague foci, Algeria

    Directory of Open Access Journals (Sweden)

    M.A. Malek

    2015-03-01

    Full Text Available In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8% rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague.

  9. Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats

    Science.gov (United States)

    Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

    2010-01-01

    Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 × 2 × 2 × 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P meat specifically increased the MDF number compared with similar non nitrite-treated meat (P = 0.03) and with similar non oxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make non promoting processed meat. PMID:20530708

  10. Investigation of computer-aided colonic crypt pattern analysis

    Science.gov (United States)

    Qi, Xin; Pan, Yinsheng; Sivak, Michael V., Jr.; Olowe, Kayode; Rollins, Andrew M.

    2007-02-01

    Colorectal cancer is the second leading cause of cancer-related death in the United States. Approximately 50% of these deaths could be prevented by earlier detection through screening. Magnification chromoendoscopy is a technique which utilizes tissue stains applied to the gastrointestinal mucosa and high-magnification endoscopy to better visualize and characterize lesions. Prior studies have shown that shapes of colonic crypts change with disease and show characteristic patterns. Current methods for assessing colonic crypt patterns are somewhat subjective and not standardized. Computerized algorithms could be used to standardize colonic crypt pattern assessment. We have imaged resected colonic mucosa in vitro (N = 70) using methylene blue dye and a surgical microscope to approximately simulate in vivo imaging with magnification chromoendoscopy. We have developed a method of computerized processing to analyze the crypt patterns in the images. The quantitative image analysis consists of three steps. First, the crypts within the region of interest of colonic tissue are semi-automatically segmented using watershed morphological processing. Second, crypt size and shape parameters are extracted from the segmented crypts. Third, each sample is assigned to a category according to the Kudo criteria. The computerized classification is validated by comparison with human classification using the Kudo classification criteria. The computerized colonic crypt pattern analysis algorithm will enable a study of in vivo magnification chromoendoscopy of colonic crypt pattern correlated with risk of colorectal cancer. This study will assess the feasibility of screening and surveillance of the colon using magnification chromoendoscopy.

  11. File list: Unc.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: His.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: His.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Unc.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: His.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Unc.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.20.AllAg.Intestinal_crypt mm9 Unclassified Digestive tract Intestinal crypt... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Dig.20.AllAg.Intestinal_crypt.bed ...

  17. Optical Aberrations and Wavefront

    Directory of Open Access Journals (Sweden)

    Nihat Polat

    2014-08-01

    Full Text Available The deviation of light to create normal retinal image in the optical system is called aberration. Aberrations are divided two subgroup: low-order aberrations (defocus: spherical and cylindrical refractive errors and high-order aberrations (coma, spherical, trefoil, tetrafoil, quadrifoil, pentafoil, secondary astigmatism. Aberrations increase with aging. Spherical aberrations are compensated by positive corneal and negative lenticular spherical aberrations in youth. Total aberrations are elevated by positive corneal and positive lenticular spherical aberrations in elderly. In this study, we aimed to analyze the basic terms regarding optic aberrations which have gained significance recently. (Turk J Ophthalmol 2014; 44: 306-11

  18. Hemangioblastic foci in human first trimester placenta: Distribution and gestational profile.

    Science.gov (United States)

    Aplin, John D; Whittaker, Hannah; Jana Lim, Yu Ting; Swietlik, Stefanie; Charnock, Jayne; Jones, Carolyn J P

    2015-10-01

    The human placenta is a site of both hematopoiesis and vasculogenesis. There are reports of hemangioblastic foci (HAF) in the first trimester placenta, but little published information about their spatiotemporal incidence. We have used semi-thin sections and whole mount staining techniques on archival early pregnancy hysterectomy material as well as freshly-collected termination tissue. We report a description of the distribution of HAF, their gestational profile, and some characteristics of the constituent cells. We show crypt-shaped HAF are present in villi at different levels from 4 to 11 weeks and in the chorionic plate from 4 to 9 weeks. In the villous placenta, the foci often approach closely at one end to the trophoblast basement membrane. Morphologically they show remarkable similarity to those found in the yolk sac at similar stages. In some crypts, all cells are CD34+, but CD34 and nestin progressively segregate into the endothelial lineage. Brachyury is present in less differentiated cells. The erythroid lineage is dominant, as shown by the widespread expression of CD235a/glycophorin and characteristic erythroid morphologies, indicating various degrees of differentiation. However, CD41 is also present in non-endothelial cells. Initially a discontinuous UEA-1/CD31-positive endothelium forms at the periphery of the foci. These cells appear to become integrated into the developing vasculogenic/angiogenic vessel network. We also demonstrate that, independent of HAF, vasculogenesis occurs near the tips of growing villi during the first trimester. We suggest HAF interface with the developing vascular network, producing communication channels that allow erythrocytes to enter the placental-embryonic circulation. We speculate that the erythroid cells act as oxygen reservoirs during the period before flow of maternal blood through the intervillous space of the placenta, allowing a slow feed of oxygen-rich cells to the developing embryo. Copyright © 2015 Elsevier

  19. Stomatal crypts may facilitate diffusion of CO(2) to adaxial mesophyll cells in thick sclerophylls.

    Science.gov (United States)

    Hassiotou, Foteini; Evans, John R; Ludwig, Martha; Veneklaas, Erik J

    2009-11-01

    In some plants, stomata are exclusively located in epidermal depressions called crypts. It has been argued that crypts function to reduce transpiration; however, the occurrence of crypts in species from both arid and wet environments suggests that crypts may play another role. The genus Banksia was chosen to examine quantitative relationships between crypt morphology and leaf structural and physiological traits to gain insight into the functional significance of crypts. Crypt resistance to water vapour and CO(2) diffusion was calculated by treating crypts as an additional boundary layer partially covering one leaf surface. Gas exchange measurements of polypropylene meshes confirmed the validity of this approach. Stomatal resistance was calculated as leaf resistance minus calculated crypt resistance. Stomata contributed significantly more than crypts to leaf resistance. Crypt depth increased and accounted for an increasing proportion of leaf resistance in species with greater leaf thickness and leaf dry mass per area. All Banksia species examined with leaves thicker than 0.6 mm had their stomata in deep crypts. We propose that crypts function to facilitate CO(2) diffusion from the abaxial surface to adaxial palisade cells in thick leaves. This and other possible functions of stomatal crypts, including a role in water use, are discussed.

  20. Association of iris crypts with acute primary angle closure.

    Science.gov (United States)

    Koh, Victor; Chua, Jacqueline; Shi, Yuan; Thakku, Sri Gowtham; Lee, Ryan; Nongpiur, Monisha E; Baskaran, Mani; Kumar, Rajesh S; Perera, Shamira; Aung, Tin; Cheng, Ching-Yu

    2017-10-01

    To determine the relationship between iris surface features and acute primary angle closure (APAC) in eyes with angle closure. Case-control study involving Asian patients diagnosed with previous APAC, primary angle closure suspect (PACS), primary angle closure (PAC) and primary angle closure glaucoma (PACG) at an eye centre in Singapore between August 2012 and January 2015. Participants underwent ophthalmic examination and digital slit-lamp iris photography. Iris surface features were graded based on crypts, furrows and colour. Fellow eyes of APAC were compared with PACS and PAC/PACG eyes with regard to their iris surface features. Occurrence of APAC. A total of 309 patients (71 APAC, 139 PACS, 47 PAC and 52 PACG) were included (mean age: 67.7±7.2 years and 36.6% male). Compared with PACS, higher crypt grade was significantly associated with lower odds of APAC (OR=0.58 for one grade higher in crypt grade; p=0.027, adjusted for age, gender, ethnicity and pupil diameter). The results remained similar when compared with PAC/PACG group (OR=0.58 for one grade higher in crypt grade; p=0.043). We did not observe any significant associations between iris furrows or colour with presence of APAC. Our study comprising Asian eyes with angle closure suggests that the presence of a higher crypt grading may be protective for APAC. As such, assessing iris surface architecture for crypts could be a new measure for risk stratification of developing APAC in eyes with angle closure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. DNA-based watermarks using the DNA-Crypt algorithm

    Directory of Open Access Journals (Sweden)

    Barnekow Angelika

    2007-05-01

    Full Text Available Abstract Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  2. DNA-based watermarks using the DNA-Crypt algorithm.

    Science.gov (United States)

    Heider, Dominik; Barnekow, Angelika

    2007-05-29

    The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  3. File list: ALL.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Pol.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: NoD.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Oth.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

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  7. File list: ALL.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

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  9. File list: NoD.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

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  10. File list: Oth.Dig.05.AllAg.Crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: His.Dig.05.AllAg.Crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: DNS.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: InP.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: ALL.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: InP.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Oth.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: DNS.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

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  19. File list: ALL.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: DNS.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

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  1. File list: Pol.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. Interphase cytogenetics of multicentric renal cell tumours confirm associations of specific aberrations with defined cytomorphologies

    OpenAIRE

    Amo-Takyi, B K; Mittermayer, C; G?nther, K; Handt, S

    2000-01-01

    To demonstrate associations of certain chromosomal aberrations with defined renal cell tumour (RCT) subtypes, we analysed 239 tumour nephrectomy cases for specimens with multicentric tumours. Chromosomal in situ hybridization was then performed on 15 cases with 34 foci (16 conventional renal cell carcinomas (RCCs), and 18 papillary RCTs (11 carcinomas and seven adenomas) for specific chromosomal aberrations, using ?-satellite probes for chromosomes 3, 7 or 17. Particular preference was given ...

  5. HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt hypertrophy to normal in jejunal mucosa.

    Science.gov (United States)

    Batman, Philip A; Kapembwa, Moses S; Belmonte, Liliana; Tudor, Gregory; Kotler, Donald P; Potten, Christopher S; Booth, Catherine; Cahn, Pedro; Griffin, George E

    2014-01-01

    To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

  6. Bringing Rad52 foci into focus

    Science.gov (United States)

    Alvaro, David; Lisby, Michael

    2011-01-01

    In 2007, we published the results of a genome-wide screen for ORFs that affect the frequency of Rad52 foci in yeast. That paper was published within the constraints of conventional online publishing tools, and it provided only a glimpse into the actual screen data. New tools in the JCB DataViewer now show how these data can—and should—be shared. PMID:21893595

  7. Foci in ray pencils of general divergency

    Directory of Open Access Journals (Sweden)

    W. F. Harris

    2009-12-01

    Full Text Available In generalized optical systems, that is, in systems which may contain thin refracting elements of asymmetric dioptric power, pencils of rays may exhibit phenomena that cannot occur in conventional optical systems.  In conventional optical systems astigmatic pencils have two principal meridians that are necessarily orthogonal; in generalized systems the principal meridians can be at any angle.  In fact in generalized systems a pencil may have only one principal meridian or even none at all.  In contrast to the line foci in the conventional interval of Sturm line foci in generalized systems may be at any angle and there may be only one line focus or no line foci.  A conventional cylindrical pencil has a single line focus at a finite distance but it can be regarded as having a second line focus at infinity.  Only in generalized systems is a single line focus possible without a second at infinity or anywhere else.  The purpose of this paper is to illustrate the types of pencils possible in generalized systems.  Particular attention is paid to the effect of including an antisymmetric component in the divergency of the pencil.

  8. Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma.

    Science.gov (United States)

    Rangaprakash, D; Dretsch, Michael N; Venkataraman, Archana; Katz, Jeffrey S; Denney, Thomas S; Deshpande, Gopikrishna

    2017-10-23

    Brain connectivity studies report group differences in pairwise connection strengths. While informative, such results are difficult to interpret since our understanding of the brain relies on region-based properties, rather than on connection information. Given that large disruptions in the brain are often caused by a few pivotal sources, we propose a novel framework to identify the sources of functional disruption from effective connectivity networks. Our approach integrates static and time-varying effective connectivity modeling in a probabilistic framework, to identify aberrant foci and the corresponding aberrant connectomics network. Using resting-state fMRI, we illustrate the utility of this novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we employed machine-learning classification to identify those significant connectivity features that possessed high predictive ability. We identified three disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant prefrontal-subcortical-parietal network of information flow. We found the MFG to be the pivotal focus of network disruption, with aberrant strength and temporal-variability of effective connectivity to the insula, amygdala and hippocampus. These connectivities also possessed high predictive ability (giving a classification accuracy of 81%); and they exhibited significant associations with symptom severity and neurocognitive functioning. In summary, dysregulation originating in the MFG caused elevated and temporally less-variable connectivity in subcortical regions, followed by a similar effect on parietal memory-related regions. This mechanism likely contributes to the reduced control over traumatic memories leading to re-experiencing, hyperarousal and flashbacks observed in soldiers with PTSD and mTBI. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley

  9. Optimally enhanced heating for focused ultrasound surgery with split foci, dual-frequency, or multi foci

    Science.gov (United States)

    Lu, Mingzhu; Guan, Yubo; Dong, Tengju; Liu, Fenfen; Wan, Mingxi

    2017-03-01

    To substantially enhance heating in HIFU treatment, several methods such as split foci, multi foci, and dual-frequency modes are used. The enhanced-cavitation heating protocols are implemented experimentally in BSA gel-phantom using four-element split-focus array. Using dual frequency of 1.2 and 2.4 MHz, the superimposing of two frequency pressures at confocal region can enhance nucleation cavitation and inertial cavitation activity. When using 135° phase shift combined with dual frequency of 1.2 and 2.4 MHz, the peak negative pressure reach maximum due to peak-negative pressures of two frequencies occur at same time, resulting strong cavitation activities. When using dual frequency of 1.2 and 2.4 MHz, 25-Hz pulse-repetition frequency (PRF), both 135° and 180° phase shift protocols, the experiment results show the largest lesion size of 10.5 × 10.5 × 11 mm3, quickest lesion inception time of less than 0.2 s, therefore, both 135° and 180° phase shift protocols are most efficient in enhanced-cavitation heating. The filtered-PCD mean square waveforms reveal that the strong inertial-cavitation activities involve in those two treatments. The lesion size of four foci of 180° phase shift, single frequency, 25 Hz PRF, is 2 times that of 0° phase shift, single frequency even if the peak intensity of 180° case is half less than that of 0° phase shift case. When arrange multi foci using phased array in a style of a wavelength distance between neighbor foci in focal plane, the result is the same as that using split foci of 180° phase shift and single frequency.

  10. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

    NARCIS (Netherlands)

    Sato, T.; van Es, J.H.; Snippert, H.J.G.; Stange, D.E.; Vries, R.G.J.; van den Born, M.M.W.; Barker, N.; Shroyer, N.F.; van de Wetering, M.L.; Clevers, H.

    2010-01-01

    Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such

  11. Diurnal variations in proliferation and crypt survival suggest a small target cell population in mouse colon

    Energy Technology Data Exchange (ETDEWEB)

    Dobbin, J.; Hamilton, E.

    1986-01-01

    Male C57BLasup(t) mice of two ages, 3-5 months (young) and 14-15 months (old) were given 11 or 15Gy whole body irradiation at different times through the day. The mice were killed after 4.5 days and the number of surviving crypts per circumference of jejunum, ileum, transverse colon and descending colon were scored. These results show crypt survival in the small and large intestine of 15-month-old mice. In the ileum the maximum crypt survival was found at 04.00 h and the minimum at 08.00 h. In the jejunum and both regions of the colon the maximum crypt survival occurred at 16.00 h. The nadir of crypt survival after 15 Gy was at 04.00 h in the jejunum and at 20.00 and 24.00 h in the transverse and descending colon, respectively. In young mice, crypt survival levels were similar to those found in old animals except at 04.00 h. when survival in the jejunum and ileum fell to 0.0004+-0.0002 and 0.0007+-0.0004, respectively. The lowest crypt survival in the colon of young mice also occurred at 04.00 h and in all four tissues the greatest number of crypts survived irradiation at 24.00 h.

  12. c-Myb is required for progenitor cell homeostasis in colonic crypts

    NARCIS (Netherlands)

    Malaterre, J.; Carpinelli, M.; Ernst, M.; Alexander, W.; Cooke, M.; Sutton, S.; Dworkin, S.; Heakth, J.K.; Frampton, J.; McArthur, G.; Clevers, J.C.; Hilton, D.; Mantamadiotis, Th.; Ramsay, R.G.

    2007-01-01

    The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar,

  13. Identifying the stem cell of the intestinal crypt: strategies and pitfalls

    NARCIS (Netherlands)

    Barker, N.; van Oudenaarden, A.; Clevers, H.

    2012-01-01

    Decades ago, two nonoverlapping crypt stem cell populations were proposed: Leblond's Crypt Base Columnar (CBC) cell and Potten's +4 cell. The identification of CBC markers including Lgr5 has confirmed Leblond's predictions that CBC cells are anatomically distinct, long-lived stem cells that

  14. Deoxycholate inhibits in vivo butyrate-mediated BrDU labeling of the colonic crypt.

    Science.gov (United States)

    Velázquez, O C; Seto, R W; Bain, A M; Fisher, J; Rombeau, J L

    1997-05-01

    The short-chain fatty acid butyrate (NaBu) selectively increases colonic crypt base proliferation and inhibits "premalignant" crypt surface hyperproliferation while the secondary bile acid deoxycholate (DCA) induces surface hyperproliferation, in vitro. We hypothesized that NaBu and DCA have similar selective and antagonistic effects on the colonic crypt proliferative pattern, in vivo. Fifty-six adult SD rats underwent surgical isolation of the colon and 24-hr intraluminal instillation with physiological (10 mM) and pharmacological (25 mM) levels of butyrate alone or combined with a physiological DCA level (5 microM). Bromodeoxyuridine-labeling indices (LI) were determined as labeled cells divided by total cells, for the whole crypt and five crypt compartments from base to surface. Treatment with NaBu increased total LI when compared to NaCl. This effect was significant only at the crypt base. Both doses of NaBu resulted in similar LI with no further response at the higher concentration. In contrast to prior in vitro studies, DCA alone at this concentration did not affect LI, but when combined with NaBu, DCA inhibited the effects of NaBu at the crypt base and surface. The conclusions are: (1) the in vivo proliferative effects of NaBu are selective to the crypt base, (2) an in vivo low physiological DCA level does not promote crypt surface hyperproliferation but does inhibit butyrate's proliferative effect, and (3) NaBu and DCA interact in a complex and antagonistic manner to selectively modulate crypt base and surface proliferation, in the rat colon, in vivo. These findings may have clinical relevance since colonic levels of NaBu and DCA are affected by diet.

  15. PMEL EcoFOCI Shelikof Line 8 Data, 1981-open

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Shelikof Line 8 Data

  16. Force Oriented Cost Information System (FOCIS) User’s Manual

    Science.gov (United States)

    2013-01-01

    list is modified to show them, as shown in Figure 8-88. In this example, another FOCIS server was found on a computer named “ TOSHIBA ”. Figure 8-88...directory for which you would need Write permission is the \\\\ Toshiba \\FOCIS\\ BACKUP directory. This is the FOCIS\\BACKUP directory on the “ Toshiba ...2. To use simple file sharing: a. On the Toshiba PC, navigate to the C:\\FOCIS\\BACKUP folder. b. Right-click on the Backup folder and select

  17. PMEL EcoFOCI Early Arctic Data, 1986-1991

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Early Arctic Data, 1987 - 1991

  18. Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress.

    Science.gov (United States)

    Zaborin, Alexander; Krezalek, Monika; Hyoju, Sanjiv; Defazio, Jennifer R; Setia, Namrata; Belogortseva, Natalia; Bindokas, Vytautas P; Guo, Qiti; Zaborina, Olga; Alverdy, John C

    2017-02-01

    Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts' microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts. Copyright © 2017 the American Physiological Society.

  19. [Establishment of DNA oxidative damage model in colorectal crypt cells by hydrogen peroxide].

    Science.gov (United States)

    Cai, Shan-rong; Zheng, Shu; Zhang, Su-zhan; Peng, Jia-ping

    2006-07-01

    To induce DNA oxidative damage in colorectal crypt cells by hydrogen peroxide in vitro. Hydrogen peroxide was diluted into 100, 50, 10, 5 and 1 micromol/L with RPMI 1640. Colorectal crypt cells were treated with peroxide for 10 min, 30 min, 1 h, 1.5 h, 12 h and 24 h respectively. The survival of colorectal crypt cell was measured by MTT method, and the DNA oxidative damage special product, 8-OhdG was detected with immunohistochemical staining. Liner regression was used to measure the time trend of survival rate with SPSS 10.0 software. Survival rate of colorectal crypt cell was 60% and 80% after 10 min of hydrogen peroxide treatment. The longer treatment of hydrogen peroxide, the lower survival rate; the survival rate was reduced to 30% in 24 h. After 10 or 30 min treatment of 100 or 50 micromol/L hydrogen peroxide, the survival rates of colorectal crypt cells were reduced by 20% compared with those of 10, 5 and 1 micromol/L hydrogen peroxide. However, while cells were treated with different concentrations of hydrogen peroxide for 1.0 h or above, there were no differences in cell survival rates. The time trend test results demonstrated that the survival rates of colorectal crypt cells treated with 10, 5 and 1 micromol/L hydrogen peroxide were significantly decreased with the time length of treatment. Colorectal crypt cells treated with different concentrations of hydrogen peroxide for 15 minutes were positively stained brown in cytoplasm and nuclear by immunohistochemistry with 8-OhdG monoclonal antibody. Hydrogen peroxide could induce DNA oxidative damage in colorectal crypt cells. And treated with 1 - 10 micromol/L hydrogen peroxide for 10 - 30 min, DNA oxidative damage is apt to be induced in colorectal crypt cell.

  20. Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.

    Directory of Open Access Journals (Sweden)

    Richard C van der Wath

    Full Text Available The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2-3 days in mice (3-5 days in humans and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the 'pedigree' and the 'niche' models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.

  1. The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

    2013-01-01

    Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...... mice and SCID mice with transfer colitis. AOM by itself did result in neither weight loss nor inflammation although treatment affected crypt widths and numbers. Although AOM together with T cell transfer did not increase the level of gut inflammation including COX-2 expression, AOM increased crypt...

  2. Cytoplasmic CUG RNA foci are insufficient to elicit key DM1 features.

    Directory of Open Access Journals (Sweden)

    Warunee Dansithong

    Full Text Available The genetic basis of myotonic dystrophy type I (DM1 is the expansion of a CTG tract located in the 3' untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG(400 repeat tract was positioned 3' of the termination codon and 5' of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA

  3. FOCIS goes south: advances in translational and clinical immunology.

    Science.gov (United States)

    Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

    2017-09-01

    FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

  4. Assembly and function of DNA double-strand break repair foci in mammalian cells

    DEFF Research Database (Denmark)

    Bekker-Jensen, Simon; Mailand, Niels

    2010-01-01

    DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks...... of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (¿-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing...... of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures....

  5. Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice.

    Science.gov (United States)

    Chen, Yun; Lee, Shih-Hua; Tsai, Ya-Hui; Tseng, Sheng-Hong

    2014-03-01

    Ischemic preconditioning (IPC) can protect against ischemia-reperfusion injury in the small intestine. Because intestinal stem cells (ISCs) control the recovery and growth of intestinal villi, this study investigated whether IPC had any effects on the activity of ISCs. The small intestines of mice were treated with IPC, laparotomy only (sham), or no surgery. The crypt fractions were isolated and the characteristics of ISCs among various groups were compared. The regenerative ability and the number of organoids grown from various crypt fractions were compared. The expression of hypoxia-inducible factor-1α (HIF-1α) and the related proteins of the Wnt-/β-catenin pathway in the crypt fractions were studied. The IPC group had higher messenger RNA levels of various stem cell markers than the sham group at days 1 and 2 after surgery. The IPC group exhibited greater regenerative activity and more crypt organoids than the sham group (P IPC-treated crypt fractions in vivo and cultured crypt organoid cells with deferoxamine-mimicked hypoxia in vitro. IPC significantly upregulated the activity of ISCs, possibly through the HIF-1α response and Wnt-/β-catenin signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Computational models reveal a passive mechanism for cell migration in the crypt.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

  7. Fluorescent foci quantitation for high-throughput analysis

    Directory of Open Access Journals (Sweden)

    Elena Ledesma-Fernández

    2015-06-01

    Full Text Available A number of cellular proteins localize to discrete foci within cells, for example DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It is often possible to measure the fluorescence emission from tagged proteins within these foci as a surrogate for the concentration of that specific protein. We wished to develop tools that would allow quantitation of fluorescence foci intensities in high-throughput studies. As proof of principle we have examined the kinetochore, a large multi-subunit complex that is critical for the accurate segregation of chromosomes during cell division. Kinetochore perturbations lead to aneuploidy, which is a hallmark of cancer cells. Hence, understanding kinetochore homeostasis and regulation are important for a global understanding of cell division and genome integrity. The 16 budding yeast kinetochores colocalize within the nucleus to form a single focus. Here we have created a set of freely-available tools to allow high-throughput quantitation of kinetochore foci fluorescence. We use this ‘FociQuant’ tool to compare methods of kinetochore quantitation and we show proof of principle that FociQuant can be used to identify changes in kinetochore protein levels in a mutant that affects kinetochore function. This analysis can be applied to any protein that forms discrete foci in cells.

  8. Quality of life in childhood epilepsy with lateralized epileptogenic foci.

    Science.gov (United States)

    Mathiak, Krystyna A; Luba, Małgorzata; Mathiak, Klaus; Karzel, Katarzyna; Wolańczyk, Tomasz; Szczepanik, Elzbieta; Ostaszewski, Paweł

    2010-08-17

    Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

  9. Dentigenous infectious foci - a risk factor of infective endocarditis.

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Krol, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-02-01

    Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis.

  10. Dentigenous infectious foci – a risk factor of infective endocarditis

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  11. Quality of life in childhood epilepsy with lateralized epileptogenic foci

    OpenAIRE

    Mathiak, Krystyna A.; Luba, Malgorzata; Mathiak, Klaus; Karzel, Katarzyna; Wolanczyk, Tomasz; Szczepanik, Elzbieta; Ostaszewski, Pawel

    2010-01-01

    Abstract Background Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. ...

  12. Understanding the persistence of plague foci in Madagascar.

    OpenAIRE

    Voahangy Andrianaivoarimanana; Katharina Kreppel; Nohal Elissa; Jean-Marc Duplantier; Elisabeth Carniel; Minoarisoa Rajerison; Ronan Jambou

    2013-01-01

    International audience; Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The bla...

  13. Quality of life in childhood epilepsy with lateralized epileptogenic foci

    Directory of Open Access Journals (Sweden)

    Mathiak Krystyna A

    2010-08-01

    Full Text Available Abstract Background Measuring quality of life (QOL helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Methods Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE. Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG examinations. Results We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p Conclusions We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

  14. Appearance of crypt neurons in the olfactory epithelium of the skate Raja clavata during development.

    Science.gov (United States)

    Ferrando, Sara; Bottaro, Massimiliano; Pedemonte, Federico; De Lorenzo, Simone; Gallus, Lorenzo; Tagliafierro, Grazia

    2007-10-01

    Crypt neurons are olfactory receptor cells located in the olfactory epithelium of fishes. They exhibit a peculiar and well-recognizable morphology, although their odorant specificity is still unknown. Data on their appearance during development are few and far between. This study set out to identify the time at which crypt neurons appeared in the skate, Raja clavata, using histological and immunohistochemical methods. For this purpose, embryos and juveniles at different stages of development, from 13 weeks after laying (11 weeks before hatching) to 24 weeks after hatching, were examined. The crypt neurons were identified on a morphological basis. An anti-alpha-tubulin antibody and two lectins (wheat germ agglutinin and peanut agglutinin) were used to highlight morphological details. The olfactory marker protein was detected by immunohistochemistry, because this protein is a marker of neuronal maturity in vertebrates. The crypt neurons could be detected by their morphology at 15 weeks after laying and became strongly olfactory marker protein immunoreactive 22 weeks after laying. Although involvement of crypt neurons in reproductive behavior has been inferred in various studies on bony fishes, their early presence in skate embryos and juveniles may suggest that they are not exclusively involved in sexual behavior. (c) 2007 Wiley-Liss, Inc.

  15. Mandibular lingual canals distribute to the dental crypts in prenatal stage.

    Science.gov (United States)

    Shiozaki, Kazunari; Fukami, Kaori; Kuribayashi, Ami; Shimoda, Shinji; Kobayashi, Kaoru

    2014-07-01

    To describe configurations of human prenatal mandibular, lingual canals using a limited-field cone beam computed tomography (CBCT) to examine their origin and anatomical significance. Nine fetal mandibles were examined using a CBCT. Mandibular maturity was assessed according to the mandibular size measured directly and image findings on development of dental crypts. Mandibular, lingual canals and the related foramina (mandibular, mental, and lingual foramina) were observed on axial, sagittal, and cross-sectional images. The horizontal position of mental and lingual foramina was assessed by direct observation using a loupe. In all nine mandibles, CBCT images depicted three separate mandibular canals, which individually occurred at the ramus area. One was a short canal directly connecting to the permanent molar crypt. The other two showed a parallel course, following the mandibular corpus toward the frontal area; the upper one connected to the mental foramen, and the lower one distributed anterior area of canine and incisor crypts. Lingual foramina were observed bilaterally in eight of nine mandibles, whose horizontal position was lingual against the crypt of deciduous canine. The lingual canals occurred from lingual foramina, and connected to the close deciduous tooth crypt or the mandibular canal distributing in the frontal area. It was suggested human dentition could be developed by plural mandibular and lingual canals.

  16. Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon

    NARCIS (Netherlands)

    Sasaki, Nobuo; Sachs, Norman; Wiebrands, Kay; Ellenbroek, Saskia I J; Fumagalli, Arianna; Lyubimova, Anna; Begthel, Harry; van den Born, Maaike; van Es, Johan H; Karthaus, Wouter R; Li, Vivian S W; López-Iglesias, Carmen; Peters, Peter J; van Rheenen, Jacco; van Oudenaarden, Alexander; Clevers, Hans

    2016-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5(+) stem cells. Whereas the colon lacks Paneth cells, deep crypt

  17. Understanding the persistence of plague foci in Madagascar.

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    2013-11-01

    Full Text Available Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  18. Understanding the persistence of plague foci in Madagascar.

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-11-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  19. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  20. Number of tumor foci predicts prognosis in papillary thyroid cancer.

    Science.gov (United States)

    Qu, Ning; Zhang, Ling; Ji, Qing-hai; Zhu, Yong-xue; Wang, Zhuo-ying; Shen, Qiang; Wang, Yu; Li, Duan-shu

    2014-12-04

    Papillary thyroid cancer (PTC) often presents as multifocal. However, the association of multifocality with poor prognosis remains controversial. The aim of this retrospective study was to identify the characteristics of PTC with multiple foci and to evaluate the association between multifocality and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as G1 (1 tumor focus), G2 (2 foci), and G3 (3 or more foci). We analyzed the clinicopathological features and clinical outcomes in each classification. A Cox regression model was used to assess the relationship between multifocality and recurrence or cancer mortality. The G1, G2 and G3 groups included 287, 141 and 68 patients, respectively. The mean age was 47.1±16.1 yr in G1, 41.1±18.4 yr in G2, and 35.5±15.9 yr in G3 and differed significantly among the 3 groups (p=0.001). The proportion of extrathyroidal extension, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) in the G1 to G3 groups increased with increasing number of tumor foci. The Kaplan-Meier curves revealed that G3 had the shortest recurrence-free survival, and differences were significant among the 3 groups (p=0.001, Log Rank test). Furthermore, cancer-specific survival rates decreased significantly with increasing number of tumor foci (p=0.041). Independent predictors of recurrence by multivariate Cox analysis included >3 tumor foci [HR 2.60, 95% confidence interval (CI) 1.53-4.39, p=0.001] and extrathyroidal extension (HR 1.95, CI 1.12-3.38, p=0.018). An increase in the number of tumors is associated with a tendency toward more aggressive features and predicts poor prognosis in PTC.

  1. Multiple hepatic foci in latent porphyria cutanea tarda

    Energy Technology Data Exchange (ETDEWEB)

    Kerjes, W.; Harder, T.; Steudel, A.; Hartlapp, J.H.

    1988-02-01

    A 41-year-old patient with latent porphyria cutanea tarda is described; 8 years after mastectomy for carcinoma, sonography and CT showed multiple hepatic foci, which were at first interpreted as liver metastases. A liver biopsy was carried out during laparoscopy and u/v fluorescence and subsequent laboratory tests confirmed the diagnosis of porphyria cutanea tarda. Treatment with Resochin produced almost complete resolution of the liver abnormalities within 9 months. Magnetic resonance tomography using proton-weighted SE sequences showed a few foci of high signal intensity.

  2. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  3. Early detection of malaria foci for targeted interventions in endemic southern Zambia

    Directory of Open Access Journals (Sweden)

    Chime Nnenna

    2011-09-01

    Full Text Available Abstract Background Zambia has achieved significant reductions in the burden of malaria through a strategy of "scaling-up" effective interventions. Progress toward ultimate malaria elimination will require sustained prevention coverage and further interruption of transmission through active strategies to identify and treat asymptomatic malaria reservoirs. A surveillance system in Zambia's Southern Province has begun to implement such an approach. An early detection system could be an additional tool to identify foci of elevated incidence for targeted intervention. Methods Based on surveillance data collected weekly from 13 rural health centres (RHCs divided into three transmission zones, early warning thresholds were created following a technique successfully implemented in Thailand. Alert levels were graphed for all 52 weeks of a year using the mean and 95% confidence interval upper limit of a Poisson distribution of the weekly diagnosed malaria cases for every available week of historic data (beginning in Aug, 2008 at each of the sites within a zone. Annually adjusted population estimates for the RHC catchment areas served as person-time of weekly exposure. The zonal threshold levels were validated against the incidence data from each of the 13 respective RHCs. Results Graphed threshold levels for the three zones generally conformed to observed seasonal incidence patterns. Comparing thresholds with historic weekly incidence values, the overall percentage of aberrant weeks ranged from 1.7% in Mbabala to 36.1% in Kamwanu. For most RHCs, the percentage of weeks above threshold was greater during the high transmission season and during the 2009 year compared to 2010. 39% of weeks breaching alert levels were part of a series of three or more consecutive aberrant weeks. Conclusions The inconsistent sensitivity of the zonal threshold levels impugns the reliability of the alert system. With more years of surveillance data available, individual

  4. Colon stem cell and crypt dynamics exposed by cell lineage reconstruction.

    Directory of Open Access Journals (Sweden)

    Yitzhak Reizel

    2011-07-01

    Full Text Available Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

  5. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

  6. Screening of Intestinal Crypt Organoids: A Simple Readout for Complex Biology.

    Science.gov (United States)

    Ley, Svenja; Galuba, Olaf; Salathe, Adrian; Melin, Nicolas; Aebi, Alexandra; Pikiolek, Monika; Knehr, Judith; Carbone, Walter; Beibel, Martin; Nigsch, Florian; Roma, Guglielmo; d'Ario, Giovanni; Kirkland, Susan; Bouchez, Laure C; Gubser Keller, Caroline; Bouwmeester, Tewis; Parker, Christian N; Ruffner, Heinz

    2017-06-01

    Oral and intestinal mucositis is a debilitating side effect of radiation treatment. A mouse model of radiation-induced mucositis leads to weight loss and tissue damage, reflecting the human ailment as it responds to keratinocyte growth factor (KGF), the standard-of-care treatment. Cultured intestinal crypt organoids allowed the development of an assay monitoring the effect of treatments of intestinal epithelium to radiation-induced damage. This in vitro assay resembles the mouse model as KGF and roof plate-specific spondin-1 (RSPO1) enhanced crypt organoid recovery following radiation. Screening identified compounds that increased the survival of organoids postradiation. Testing of these compounds revealed that the organoids changed their responses over time. Unbiased transcriptome analysis was performed on crypt organoid cultures at various time points in culture to investigate this adaptive behavior. A number of genes and pathways were found to be modulated over time, providing a rationale for the altered sensitivity of the organoid cultures. This report describes an in vitro assay that reflects aspects of human disease. The assay was used to identify bioactive compounds, which served as probes to interrogate the biology of crypt organoids over prolonged culture. The pathways that are changing over time may offer potential targets for treatment of mucositis.

  7. Differential proteome analysis along jejunal crypt-villus axis in piglets.

    Science.gov (United States)

    Xiong, Xia; Yang, Huansheng; Hu, Xihai; Wang, Xiaocheng; Li, Biao; Long, Lina; Li, Tiejun; Wang, Junjun; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2016-01-01

    The brush-border membrane (BBM) of enterocytes is responsible for the digestion and absorption of nutrients and ions in the small intestine. To identify the BBM proteins involved in epithelial cell maturation along the crypt-villus axis, enterocytes were sequentially isolated from the villus tip to the crypt of the jejunum from 21-day-old suckling piglets. After preparation of BBM vesicles, we detected 194 proteins in the jejunal epithelial cells by isobaric tags using relative and absolute quantification (iTRAQ) techniques. Of these, 56 BBM proteins were differentially expressed along the crypt-villus axis. During differentiation, the expression of proteins related to digestion and absorption of nutrients was primarily downregulated at the upper, middle villus, or crypt compared to the villus tip, while expression of proteins related to structural and enzyme regulator proteins was largely upregulated. We verified the differences in Na(+)/K(+) -transporting ATPase, galectin-3, and an intestinal-type fatty acid binding protein by western blot or immunochemical analysis. Identification of BBM-associated proteins helps enhance our understanding of digestion and absorption in piglets and other mammals, including humans.

  8. Bionomics of Geohelminth Nematodes in Contaminated Foci in ...

    African Journals Online (AJOL)

    A combined field and laboratory investigation was conducted on the bionomics of geohelminths in contaminated foci in Abua communities using the Cobb's decanting and sieving method. The result of the study showed that eggs of Ascaris lumbricoides were 262 (44%), hookworm, 173 (29%) and Trichuris trichiura, 102 ...

  9. Bionomics of Geohelminth Nematodes in Contaminated Foci in ...

    African Journals Online (AJOL)

    Michael Horsfall

    ABSTRACT: A combined field and laboratory investigation was conducted on the bionomics of geohelminths in contaminated foci in Abua communities using the Cobb's decanting and sieving method. The result of the study showed that eggs of Ascaris lumbricoides were 262 (44%), hookworm, 173 (29%) and Trichuris ...

  10. Characterization of Aes nuclear foci in colorectal cancer cells.

    Science.gov (United States)

    Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M Mark

    2016-01-01

    Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  11. Leptin, cell proliferation and crypt fission in the gastrointestinal tract of intravenously fed rats.

    Science.gov (United States)

    FitzGerald, A J; Mandir, N; Goodlad, R A

    2005-02-01

    Many peptides, hormones and growth factors have been implicated in the control of cell renewal in the gastrointestinal epithelium. Leptin is present in the stomach and salivary glands and leptin receptors are seen throughout the gut. Leptin can stimulate mitogen-activated protein kinase activity in vitro and short-term infusion has been reported to have a proliferative action on the colon in vivo, suggesting a biological link between obesity, physical activity and colon cancer. Food intake is one of the most important determinants of intestinal mucosal cell renewal, thus any direct effects of leptin on the gut may be hidden. This problem has been avoided experimentally by maintaining animals on total parenteral nutrition (TPN). Male Wistar rats were anaesthetized and cannulae were inserted into the jugular vein to deliver the TPN diet to which had been added 0, 0.5, 2.5, or 10 mg/kg of recombinant murine leptin. Orally fed rats were also studied. After 6 days of treatment, all animals were injected with vincristine and killed 2 h later. Tissue weight was recorded and crypt cell proliferation (arrested metaphases) and crypt fission were scored in 'microdissected' crypts. Leptin infusion led to a small decrease in body weight and in the weight of the caecum. Intestinal cell proliferation was significantly reduced by TPN when compared to the orally fed rats, but the addition of leptin had no effect on the small intestine or colon. Crypt fission was also significantly lowered in the TPN group. Fission was slightly but significantly increased in the proximal and mid-colon of the leptin-treated rats, but was decreased in the distal colon. Although leptin did not significantly alter cell proliferation, it had significant effects on the process of crypt fission in the colon, which varied according to the exact locality.

  12. A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt

    KAUST Repository

    Mirams, Gary R.

    2012-11-01

    The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal cancer arises due to mutations that disrupt the normal cellular dynamics of the crypts. Using a spatially structured cell-based model of a colonic crypt, we investigate the likelihood that the progeny of a mutated cell will dominate, or be sloughed out of, a crypt. Our approach is to perform multiple simulations, varying the spatial location of the initial mutation, and the proliferative and adhesive properties of the mutant cells, to obtain statistical distributions for the probability of their domination. Our simulations lead us to make a number of predictions. The process of monoclonal conversion always occurs, and does not require that the cell which initially gave rise to the population remains in the crypt. Mutations occurring more than one to two cells from the base of the crypt are unlikely to become the dominant clone. The probability of a mutant clone persisting in the crypt is sensitive to dysregulation of adhesion. By comparing simulation results with those from a simple one-dimensional stochastic model of population dynamics at the base of the crypt, we infer that this sensitivity is due to direct competition between wild-type and mutant cells at the base of the crypt. We also predict that increases in the extent of the spatial domain in which the mutant cells proliferate can give rise to counter-intuitive, non-linear changes to the probability of their fixation, due to effects that cannot be captured in simpler models. © 2012 Elsevier Ltd.

  13. The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis.

    Directory of Open Access Journals (Sweden)

    Huijing Du

    2015-08-01

    Full Text Available The epithelium of the small intestinal crypt, which has a vital role in protecting the underlying tissue from the harsh intestinal environment, is completely renewed every 4-5 days by a small pool of stem cells at the base of each crypt. How is this renewal controlled and homeostasis maintained, particularly given the rapid nature of this process? Here, based on the recent observations from in vitro "mini gut" studies, we use a hybrid stochastic model of the crypt to investigate how exogenous niche signaling (from Wnt and BMP combines with auto-regulation to promote homeostasis. This model builds on the sub-cellular element method to account for the three-dimensional structure of the crypt, external regulation by Wnt and BMP, internal regulation by Notch signaling, as well as regulation by internally generated diffusible signals. Results show that Paneth cell derived Wnt signals, which have been observed experimentally to sustain crypts in cultured organs, have a dramatically different influence on niche dynamics than does mesenchyme derived Wnt. While this signaling can indeed act as a redundant backup to the exogenous gradient, it introduces a positive feedback that destabilizes the niche and causes its uncontrolled expansion. We find that in this setting, BMP has a critical role in constraining this expansion, consistent with observations that its removal leads to crypt fission. Further results also point to a new hypothesis for the role of Ephrin mediated motility of Paneth cells, specifically that it is required to constrain niche expansion and maintain the crypt's spatial structure. Combined, these provide an alternative view of crypt homeostasis where the niche is in a constant state of expansion and the spatial structure of the crypt arises as a balance between this expansion and the action of various sources of negative regulation that hold it in check.

  14. The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis.

    Science.gov (United States)

    Du, Huijing; Nie, Qing; Holmes, William R

    2015-08-01

    The epithelium of the small intestinal crypt, which has a vital role in protecting the underlying tissue from the harsh intestinal environment, is completely renewed every 4-5 days by a small pool of stem cells at the base of each crypt. How is this renewal controlled and homeostasis maintained, particularly given the rapid nature of this process? Here, based on the recent observations from in vitro "mini gut" studies, we use a hybrid stochastic model of the crypt to investigate how exogenous niche signaling (from Wnt and BMP) combines with auto-regulation to promote homeostasis. This model builds on the sub-cellular element method to account for the three-dimensional structure of the crypt, external regulation by Wnt and BMP, internal regulation by Notch signaling, as well as regulation by internally generated diffusible signals. Results show that Paneth cell derived Wnt signals, which have been observed experimentally to sustain crypts in cultured organs, have a dramatically different influence on niche dynamics than does mesenchyme derived Wnt. While this signaling can indeed act as a redundant backup to the exogenous gradient, it introduces a positive feedback that destabilizes the niche and causes its uncontrolled expansion. We find that in this setting, BMP has a critical role in constraining this expansion, consistent with observations that its removal leads to crypt fission. Further results also point to a new hypothesis for the role of Ephrin mediated motility of Paneth cells, specifically that it is required to constrain niche expansion and maintain the crypt's spatial structure. Combined, these provide an alternative view of crypt homeostasis where the niche is in a constant state of expansion and the spatial structure of the crypt arises as a balance between this expansion and the action of various sources of negative regulation that hold it in check.

  15. Spherical aberration in contact lens wear.

    Science.gov (United States)

    Lindskoog Pettersson, A; Jarkö, C; Alvin, A; Unsbo, P; Brautaset, R

    2008-08-01

    The aim of the present studies was to investigate the effect on spherical aberration of different non custom-made contact lenses, both with and without aberration control. A wavefront analyser (Zywave, Bausch & Lomb) was used to measure the aberrations in each subject's right eye uncorrected and with the different contact lenses. The first study evaluated residual spherical aberration with a standard lens (Focus Dailies Disposable, Ciba Vision) and with an aberration controlled contact lens (ACCL) (Definition AC, Optical Connection Inc.). The second study evaluated the residual spherical aberrations with a monthly disposable silicone hydrogel lens with aberration reduction (PureVision, Bausch & Lomb). Uncorrected spherical aberration was positive for all pupil sizes in both studies. In the first study, residual spherical aberration was close to zero with the standard lens for all pupil sizes whereas the ACCL over-corrected spherical aberration. The results of the second study showed that the monthly disposable lens also over-corrected the aberration making it negative. The changes in aberration were statistically significant (plenses. Since the amount of aberration varies individually we suggest that aberrations should be measured with lenses on the eye if the aim is to change spherical aberration in a certain direction.

  16. PMEL EcoFOCI Chukchi Sea profile data, 2010-2012

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Chukchi Sea. PMEL EcoFOCI data from a local source.

  17. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  18. Reliability of seizure semiology in patients with 2 seizure foci.

    Science.gov (United States)

    Rathke, Kevin M; Schäuble, Barbara; Fessler, A James; So, Elson L

    2011-06-01

    To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient. Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs). Epilepsy monitoring unit of referral comprehensive epilepsy program. Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years. The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread. Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test). Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

  19. Appropriate Crypt Formation in the Uterus for Embryo Homing and Implantation Requires Wnt5a-ROR Signaling

    Directory of Open Access Journals (Sweden)

    Jeeyeon Cha

    2014-07-01

    Full Text Available Embryo homing and implantation occur within a crypt (implantation chamber at the antimesometrial (AM pole along the uterus. The mechanism by which this is achieved is not known. Here, we show that villi-like epithelial projections from the main uterine lumen toward the AM pole at regularly spaced intervals that form crypts for embryo implantation were disrupted in mice with uterine loss or gain of function of Wnt5a, or loss of function of both Ror1 and Ror2. This disruption of Wnt5a-ROR signaling resulted in disorderly epithelial projections, crypt formation, embryo spacing, and impaired implantation. These early disturbances under abnormal Wnt5a-ROR signaling were reflected in adverse late pregnancy events, including defective decidualization and placentation, ultimately leading to compromised pregnancy outcomes. This study presents deeper insight regarding the formation of organized epithelial projections for crypt formation and embryo implantation for pregnancy success.

  20. IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations

    Science.gov (United States)

    Van Landeghem, Laurianne; Santoro, M. Agostina; Mah, Amanda T.; Krebs, Adrienne E.; Dehmer, Jeffrey J.; McNaughton, Kirk K.; Helmrath, Michael A.; Magness, Scott T.; Lund, P. Kay

    2015-01-01

    Insulin-like growth factor 1 (IGF1) has potent trophic effects on normal or injured intestinal epithelium, but specific effects on intestinal stem cells (ISCs) are undefined. We used Sox9-enhanced green fluorescent protein (EGFP) reporter mice that permit analyses of both actively cycling ISCs (Sox9-EGFPLow) and reserve/facultative ISCs (Sox9-EGFPHigh) to study IGF1 action on ISCs in normal intestine or during crypt regeneration after high-dose radiation-induced injury. We hypothesized that IGF1 differentially regulates proliferation and gene expression in actively cycling and reserve/facultative ISCs. IGF1 was delivered for 5 days using subcutaneously implanted mini-pumps in uninjured mice or after 14 Gy abdominal radiation. ISC numbers, proliferation, and transcriptome were assessed. IGF1 increased epithelial growth in nonirradiated mice and enhanced crypt regeneration after radiation. In uninjured and regenerating intestines, IGF1 increased total numbers of Sox9-EGFPLow ISCs and percentage of these cells in M-phase. IGF1 increased percentages of Sox9-EGFPHigh ISCs in S-phase but did not expand this population. Microarray revealed that IGF1 activated distinct gene expression signatures in the 2 Sox9-EGFP ISC populations. In vitro IGF1 enhanced enteroid formation by Sox9-EGFPHigh facultative ISCs but not Sox9-EGFPLow actively cycling ISCs. Our data provide new evidence that IGF1 activates 2 ISC populations via distinct regulatory pathways to promote growth of normal intestinal epithelium and crypt regeneration after irradiation.—Van Landeghem, L., Santoro, M. A., Mah, A. T., Krebs, A. E., Dehmer, J. J., McNaughton, K. K., Helmrath, M. A., Magness, S. T., Lund, P. K. IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations. PMID:25837582

  1. The effect of ginkgo biloba extract on radiosensitivity of mouse skin and jejunal crypt

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Hwan; Ha, Sung Whan [Seoul National Univ. Medical College, Seoul (Korea, Republic of)

    1998-06-01

    Ginkgo biloba extract(GBE) is known to increase the peripheral blood circulation. This study was designed to evaluate the effect of GBE on the acute normal tissue radiation reaction. C3H mice were divided into two groups, radiation alone and two doses GBE plus radiation, for both acute skin reaction and jejunal crypt assay. GBE was given i.p. one hour before irradiation with priming dose given one day earlier. Thirty to Fifty Gy for acute skin reaction and 11 to 14 Gy for jejunal crypt were irradiated to right hind leg and whole body, respectively. Radiation doses(RD{sub 50}) for peak skin score of 2.0 were 44.2Gy(40.6-48.2Gy) for radiation alone and 44.4Gy(41.6-47.4Gy) for two doses GBE plus radiation, showing no effect of GBE on acute radiation skin damage. The numbers of regenerating jejunal crypts per circumference were also almost the same for each radiation dose level(p=0.57-0.94), and the mean lethal doses(D{sub o}) were 1.80Gy(1.57-2.09Gy) for radiation alone and 1.88Gy(1.65-2.18Gy) for two doses GBE plus radiation, indicating no effect of GBE on jejunal crypt cell survival after radiation. GBE doesn't increase acute normal tissue radiation reaction in this model system. As GBE was verified to enhance radiation effect on tumor, high therapeutic gain is expected when GBE is combined with radiation therapy.

  2. Modelling the spatio-temporal cell dynamics reveals novel insights on cell differentiation and proliferation in the small intestinal crypt.

    Directory of Open Access Journals (Sweden)

    Carmen Pin

    Full Text Available We developed a slow structural relaxation model to describe cellular dynamics in the crypt of the mouse small intestine. Cells are arranged in a three dimensional spiral the size of which dynamically changes according to cell production demands of adjacent villi. Cell differentiation and proliferation is regulated through Wnt and Notch signals, the strength of which depends on the local cell composition. The highest level of Wnt activity is associated with maintaining equipotent stem cells (SC, Paneth cells and common goblet-Paneth cell progenitors (CGPCPs intermingling at the crypt bottom. Low levels of Wnt signalling area are associated with stem cells giving rise to secretory cells (CGPCPs, enteroendocrine or Tuft cells and proliferative absorptive progenitors. Deciding between these two fates, secretory and stem/absorptive cells, depends on Notch signalling. Our model predicts that Notch signalling inhibits secretory fate if more than 50% of cells they are in contact with belong to the secretory lineage. CGPCPs under high Wnt signalling will differentiate into Paneth cells while those migrating out from the crypt bottom differentiate into goblet cells. We have assumed that mature Paneth cells migrating upwards undergo anoikis. Structural relaxation explains the localisation of Paneth cells to the crypt bottom in the absence of active forces. The predicted crypt generation time from one SC is 4-5 days with 10-12 days needed to reach a structural steady state. Our predictions are consistent with experimental observations made under altered Wnt and Notch signalling. Mutations affecting stem cells located at the crypt floor have a 50% chance of being propagated throughout the crypt while mutations in cells above are rarely propagated. The predicted recovery time of an injured crypt losing half of its cells is approximately 2 days.

  3. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.

    Science.gov (United States)

    Parker, Aimee; Maclaren, Oliver J; Fletcher, Alexander G; Muraro, Daniele; Kreuzaler, Peter A; Byrne, Helen M; Maini, Philip K; Watson, Alastair J M; Pin, Carmen

    2017-02-01

    The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced and when it is temporarily halted. We found that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.-Parker, A., Maclaren, O. J., Fletcher, A. G., Muraro, D., Kreuzaler, P. A., Byrne, H. M., Maini, P. K., Watson, A. J. M., Pin, C. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi. © The Author(s).

  4. The Art of Optical Aberrations

    Science.gov (United States)

    Wylde, Clarissa Eileen Kenney

    Art and optics are inseparable. Though seemingly opposite disciplines, the combination of art and optics has significantly impacted both culture and science as they are now known. As history has run its course, in the sciences, arts, and their fruitful combinations, optical aberrations have proved to be a problematic hindrance to progress. In an effort to eradicate aberrations the simple beauty of these aberrational forms has been labeled as undesirable and discarded. Here, rather than approach aberrations as erroneous, these beautiful forms are elevated to be the photographic subject in a new body of work, On the Bright Side. Though many recording methods could be utilized, this work was composed on classic, medium-format, photographic film using white-light, Michelson interferometry. The resulting images are both a representation of the true light rays that interacted on the distorted mirror surfaces (data) and the artist's compositional eye for what parts of the interferogram are chosen and displayed. A detailed description of the captivating interdisciplinary procedure is documented and presented alongside the final artwork, CCD digital reference images, and deformable mirror contour maps. This alluring marriage between the arts and sciences opens up a heretofore minimally explored aspect of the inextricable art-optics connection. It additionally provides a fascinating new conversation on the importance of light and optics in photographic composition.

  5. The effect of kefir on glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) levels in mice with colonic abnormal crypt formation (ACF) induced by azoxymethane (AOM).

    Science.gov (United States)

    Cenesiz, S; Devrim, A K; Kamber, U; Sozmen, M

    2008-01-01

    In this study we investigated the effect of kefir on the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) in the liver, stomach, spleen and colon of mice with colonic aberrant crypts formed by azoxymethane (AOM). Thirty 12 weeks old Swiss Albino mice averaging 31.5 g weight were used as experimental animals. The mice were separated into 3 groups. The first group was the control group, second group was the AOM and third group was the AOM+kefir group. We applied AOM to the second and third groups. Mice were fed ad libitum by laboratory rodent chow during the experiment period. Water was given to the first and second groups and third group received only kefir diluted with water (50%). AOM was injected subcutaneously to the second and third groups for 7 weeks (two times a week, 5 mg/kg). Six weeks after the final AOM treatment the animals were sacrificed and liver, stomach, spleen and colon samples were collected from all the groups. MDA level demonstrated an increase only in stomach for the third group (p kefir plays an antioxidant role.

  6. Phase Aberrations in Diffraction Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Marchesini, S; Chapman, H N; Barty, A; Howells, M R; Spence, J H; Cui, C; Weierstall, U; Minor, A M

    2005-09-29

    In coherent X-ray diffraction microscopy the diffraction pattern generated by a sample illuminated with coherent x-rays is recorded, and a computer algorithm recovers the unmeasured phases to synthesize an image. By avoiding the use of a lens the resolution is limited, in principle, only by the largest scattering angles recorded. However, the imaging task is shifted from the experiment to the computer, and the algorithm's ability to recover meaningful images in the presence of noise and limited prior knowledge may produce aberrations in the reconstructed image. We analyze the low order aberrations produced by our phase retrieval algorithms. We present two methods to improve the accuracy and stability of reconstructions.

  7. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  8. RGD-Dependent Epithelial Cell-Matrix Interactions in the Human Intestinal Crypt

    Directory of Open Access Journals (Sweden)

    Yannick D. Benoit

    2012-01-01

    Full Text Available Interactions between the extracellular matrix (ECM and integrin receptors trigger structural and functional bonds between the cell microenvironment and the cytoskeleton. Such connections are essential for adhesion structure integrity and are key players in regulating transduction of specific intracellular signals, which in turn regulate the organization of the cell microenvironment and, consequently, cell function. The RGD peptide-dependent integrins represent a key subgroup of ECM receptors involved in the maintenance of epithelial homeostasis. Here we review recent findings on RGD-dependent ECM-integrin interactions and their roles in human intestinal epithelial crypt cells.

  9. Coevolved crypts and exocrine glands support mutualistic bacteria in fungus-growing ants

    DEFF Research Database (Denmark)

    Currie, Cameron R; Poulsen, Michael; Mendenhall, John

    2006-01-01

    that ants rear the antibiotic-producing bacteria in elaborate cuticular crypts, supported by unique exocrine glands, and that these structures have been highly modified across the ants' evolutionary history. This specialized structural evolution, together with the absence of these bacteria and modifications......Attine ants engage in a quadripartite symbiosis with fungi they cultivate for food, specialized garden parasites, and parasite-inhibiting bacteria. Molecular phylogenetic evidence supports an ancient host-pathogen association between the ant-cultivar mutualism and the garden parasite. Here we show...

  10. A national register of historic and contemporary anthrax foci.

    Science.gov (United States)

    Cherkasskiy, B L

    1999-08-01

    Anthrax in Russia has for a long time posed a serious problem for public health and veterinary services. At the beginning of the century, 40-60 thousand cases of this infection were annually reported in the country in agricultural animals and about 10-20 thousand cases in people where each fourth (25%) was dying. In the Russian Federation the registration of anthrax foci is obligatory for veterinary as well as for sanitary-epidemiological services. So our initial project, funded by the International Technical and Scientific Center in Moscow, has envisaged the collection of all data of known anthrax foci, including the village name, agricultural council, region, oblast and year of occurrence. The objective is to assemble a reference handbook, "Register of stable anthrax sites in the Russian Federation", containing organized information on more than 10 000 anthrax foci occurring during the past 100 years. Such a study makes it possible to identify regions characterized by the highest concentrations of stationary anthrax sites in Russia, to identify trends in expressed activity of such sites through the periodic emergence of disease in humans and animals, and to determine the factors contributing to the formation of such trends. In doing this, it makes it possible to develop contingency plans for different risk locations (i.e. high risk of persistent infection, high risk of sporadic occurrence, low risk areas, etc.) in terms of anthrax in Russia, to identify high risk areas and develop a differentiated strategy of vaccination and other control strategies, and to develop preventive recommendations to reduce risk in high risk areas. It is now important to develop the second step of the project: to develop in depth studies of particular clusters to determine which factors are associated with Russian anthrax outbreaks. Maps will greatly enhance the value of this work in terms of spatial analysis. Furthermore, this supplementary project will allow the incorporation of

  11. Ocular aberrations and wavefront aberrometry: A review

    Directory of Open Access Journals (Sweden)

    Holly A. Unterhorst

    2015-03-01

    Full Text Available Wavefront aberrations can be described as deviations of the wavefront exiting the eye froma reference wavefront that is aberration free and diffraction limited. Ocular aberrations canbe sub-categorised as lower and higher order aberrations. Ocular aberrations have promptedinterest amongst the ocular healthcare community owing to their influences on the visualfunctioning of patients as well as differences observed in ocular aberrations through the useof refractive surgery both pre- and post-operatively. Uncompensated refractive error remainsone of the most common reasons for which patients consult optometrists. Compensationof refractive error, or lower order aberrations, has become a routine procedure during anoptometric examination. However, there are some patients who experience visual symptomseven after their refractive errors have been compensated via spectacles or contact lenses.Higher-order aberrations may be the source of these visual disturbances. Refractive surgeryhas been found to influence and even induce various changes in higher-order aberrationspost-operatively, which in turn has led to increased interest in wavefront aberrations and howthe measurement of these aberrations can improve diagnosis and treatment within optometryand ophthalmology.

  12. ANALYSIS OF TUBERCULOSIS INCIDENCE IN THE INFECTIOUS FOCI IN DAGESTAN REPUBLIC

    Directory of Open Access Journals (Sweden)

    T. G. Gireev

    2017-01-01

    Full Text Available This research is based on the investigation in 144 tuberculous foci and examination of 272 persons living in those foci and contacting with tuberculosis cases. It has been found out that outside tuberculous infectious foci a significant number of people is still exposed to tuberculous infection. During 5 years the average annual incidence in those exposed to tuberculous infection made 1176.5 per 100,000 pop., which is 32.2 fold higher than the rate for general population. In order to enhance efficiency of tuberculosis control activities in infectious tuberculous foci it is feasible to increase the territory coverage and duration of follow-up period.

  13. De Novo Formation of Insulin-Producing “Neo-β Cell Islets” from Intestinal Crypts

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    2014-03-01

    Full Text Available The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell “reprogramming factors” in a wide spectrum of tissues. We report that transient intestinal expression of these factors—Pdx1, MafA, and Ngn3 (PMN—promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into “neoislets” below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal “organoids” stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

  14. Phylogenetically Diverse Burkholderia Associated with Midgut Crypts of Spurge Bugs, Dicranocephalus spp. (Heteroptera: Stenocephalidae).

    Science.gov (United States)

    Kuechler, Stefan Martin; Matsuura, Yu; Dettner, Konrad; Kikuchi, Yoshitomo

    2016-06-25

    Diverse phytophagous heteropteran insects, commonly known as stinkbugs, are associated with specific gut symbiotic bacteria, which have been found in midgut cryptic spaces. Recent studies have revealed that members of the stinkbug families Coreidae and Alydidae of the superfamily Coreoidea are consistently associated with a specific group of the betaproteobacterial genus Burkholderia, called the "stinkbug-associated beneficial and environmental (SBE)" group, and horizontally acquire specific symbionts from the environment every generation. However, the symbiotic system of another coreoid family, Stenocephalidae remains undetermined. We herein investigated four species of the stenocephalid genus Dicranocephalus. Examinations via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) revealed the typical arrangement and ultrastructures of midgut crypts and gut symbionts. Cloning and molecular phylogenetic analyses of bacterial genes showed that the midgut crypts of all species are colonized by Burkholderia strains, which were further assigned to different subgroups of the genus Burkholderia. In addition to the SBE-group Burkholderia, a number of stenocephalid symbionts belonged to a novel clade containing B. sordidicola and B. udeis, suggesting a specific symbiont clade for the Stenocephalidae. The symbiotic systems of stenocephalid bugs may provide a unique opportunity to study the ongoing evolution of symbiont associations in the stinkbug-Burkholderia interaction.

  15. Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data.

    Science.gov (United States)

    Ruktanonchai, Nick W; DeLeenheer, Patrick; Tatem, Andrew J; Alegana, Victor A; Caughlin, T Trevor; Zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W; Smith, David L

    2016-04-01

    Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.

  16. Phase and birefringence aberration correction

    Science.gov (United States)

    Bowers, M.; Hankla, A.

    1996-07-09

    A Brillouin enhanced four wave mixing phase conjugate mirror corrects phase aberrations of a coherent electromagnetic beam and birefringence induced upon that beam. The stimulated Brillouin scattering (SBS) phase conjugation technique is augmented to include Brillouin enhanced four wave mixing (BEFWM). A seed beam is generated by a main oscillator which arrives at the phase conjugate cell before the signal beams in order to initiate the Brillouin effect. The signal beam which is being amplified through the amplifier chain is split into two perpendicularly polarized beams. One of the two beams is chosen to be the same polarization as some component of the seed beam, the other orthogonal to the first. The polarization of the orthogonal beam is then rotated 90{degree} such that it is parallel to the other signal beam. The three beams are then focused into cell containing a medium capable of Brillouin excitation. The two signal beams are focused such that they cross the seed beam path before their respective beam waists in order to achieve BEFWM or the two signal beams are focused to a point or points contained within the focused cone angle of the seed beam to achieve seeded SBS, and thus negate the effects of all birefringent and material aberrations in the system. 5 figs.

  17. Aberrations of magnetooptical system of SALO recirculator

    Science.gov (United States)

    Guk, I. S.; Dovbnya, A. N.; Kononenko, S. G.; Peev, F. A.; Tarasenko, A. S.

    2010-12-01

    The influence of spatial and chromatic aberrations on the parameters of the 730 MeV beam extracted from a SALO recirculator is studied using numerical simulation. The influence of fringing fields and the heterogeneity of the guide field of dipole magnets on the beam parameters at the extraction point is studied for different orders and types of aberrations. Estimates of the contributions of the different types of aberrations to the extracted beam emittance are presented.

  18. Effect of dibutylnitrosamine and saccharin on glutamyl transpeptidase-positive foci and liver cancer.

    OpenAIRE

    Pereira, M A; Herren, S L; Britt, A L

    1983-01-01

    Consistent with the proposed precursor relationship of GGTase-positive foci to hepatocarcinogenesis, the induction of foci by DBN was associated with the induction of hyperplastic nodules and hepatocellular carcinoma and the concurrent administration of sodium saccharin in the diet with DBN in the drinking water increased the tumorigenic response in the liver to DBN. Images FIGURE 1. FIGURE 3. FIGURE 4.

  19. Measurement of the cell membrane capacitance and conductance of colonic crypt cells of the rat using the patch clamp technique

    CERN Document Server

    Schill, C

    2005-01-01

    Using the patch clamp technique the membrane capacitance and membrane conductance of colonic crypt cells of the rat was measured. The influence of the intracellular agonists Ca++, cAMP and of osmotic changes on the membrane capacitance and conductance was studied.

  20. Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling.

    Science.gov (United States)

    Cha, Jeeyeon; Bartos, Amanda; Park, Craig; Sun, Xiaofei; Li, Yingju; Cha, Sang-Wook; Ajima, Rieko; Ho, Hsin-Yi Henry; Yamaguchi, Terry P; Dey, Sudhansu K

    2014-07-24

    Embryo homing and implantation occur within a crypt (implantation chamber) at the antimesometrial (AM) pole along the uterus. The mechanism by which this is achieved is not known. Here, we show that villi-like epithelial projections from the main uterine lumen toward the AM pole at regularly spaced intervals that form crypts for embryo implantation were disrupted in mice with uterine loss or gain of function of Wnt5a, or loss of function of both Ror1 and Ror2. This disruption of Wnt5a-ROR signaling resulted in disorderly epithelial projections, crypt formation, embryo spacing, and impaired implantation. These early disturbances under abnormal Wnt5a-ROR signaling were reflected in adverse late pregnancy events, including defective decidualization and placentation, ultimately leading to compromised pregnancy outcomes. This study presents deeper insight regarding the formation of organized epithelial projections for crypt formation and embryo implantation for pregnancy success. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Stem cell differentiation as a renewal-reward process: predictions and validation in the colonic crypt.

    Science.gov (United States)

    Vanaja, Kiran Gireesan; Feinberg, Andrew P; Levchenko, Andre

    2012-01-01

    Stem cells serve as persistent reservoirs for replenishment of rapidly renewing tissues, frequently also ensuring that the correct tissue morphology is maintained. This process is inherently stochastic due to the small number and stochastic division patterns within the stem cell compartments, as well as the essentially stochastic differentiation events that follow the initial stem cell expansion. Here we propose a new formalism to describe this process, by employing the approach known in statistics as the renewal-reward process. Using this approximation allows application of the mathematical apparatus developed for renewal-reward processes to the stochastic stem cell biology. We show in the context of colonic crypts that the resulting predictions match the experimental results, while also providing a convenient tool for analysis of normal and abnormal differentiation processes.

  2. The effects of herbs on the radiation-induced apoptosis in intestinal crypt cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; An, Mi Ra; Nah, Seung Yeol; Lee, Jong Hwan; Kim, Jae Ha; Shin, Dong Ho [Chonnam National Univ., Gwangju (Korea, Republic of); Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of); Jang, Jong Sik [Sangju National Univ., Sangju (Korea, Republic of)

    2001-03-15

    This study was performed to determine the effect of several herbs on radiation-induced apoptosis in jejunal crypt cells. Longyanrou(Euphoris logana), Suanzaoren(Zizyphus vulgaris), Yuanzhi(Polygala tenuifolia), Rensan(Panax ginseng), Fuling(Poria cocos), Muxiang(Saussurea lappa), Chuanxiong(Cnidium offcinale), Baishaoyao(Paeonia lactifolia), Shengma(Cimicifuga heracleifolia), Chaihu(Bupleurum falcatum) and Dongchongxiacao(Paecilomyces japonica) reduced the frequency of radiation-induced apoptosis(p<0.05). Although the mechanisms of this effect remain to be elucidated, these results indicated that Longyanrou, Suanzaoren, Yuanzhi, Rensan, Fuling, Muxiang, Chuanxiong, Baishaoyao, Shengma, Chaihu and Dongchongxiacao might be useful inhibitors of apoptosis, especially since these are relative nontoxic natural products.

  3. Aberrant Radial Artery Causing Carpal Tunnel Syndrome

    Directory of Open Access Journals (Sweden)

    Zinon T. Kokkalis

    2016-07-01

    Full Text Available Anatomical vascular variations are rare causes of carpal tunnel syndrome. An aberrant medial artery is the most common vascular variation, while an aberrant radial artery causing carpal tunnel syndrome is even more rare, with an incidence ranging less than 3%. This article reports a patient with compression of the median nerve at the carpal tunnel by an aberrant superficial branch of the radial artery. An 80- year- old man presented with a 5-year history of right hand carpal tunnel syndrome; Tinel sign, Phalen test and neurophysiological studies were positive. Open carpal tunnel release showed an aberrant superficial branch of the radial artery with its accompanying veins running from radially to medially, almost parallel to the median nerve, ending at the superficial palmar arterial arch. The median nerve was decompressed without ligating the aberrant artery. At the last follow-up, 2 years after diagnosis and treatment the patient is asymptomatic.

  4. Aberrant Radial Artery Causing Carpal Tunnel Syndrome.

    Science.gov (United States)

    Kokkalis, Zinon T; Tolis, Konstantinos E; Megaloikonomos, Panayiotis D; Panagopoulos, Georgios N; Igoumenou, Vasilios G; Mavrogenis, Andreas F

    2016-06-01

    Anatomical vascular variations are rare causes of carpal tunnel syndrome. An aberrant medial artery is the most common vascular variation, while an aberrant radial artery causing carpal tunnel syndrome is even more rare, with an incidence ranging less than 3%. This article reports a patient with compression of the median nerve at the carpal tunnel by an aberrant superficial branch of the radial artery. An 80- year- old man presented with a 5-year history of right hand carpal tunnel syndrome; Tinel sign, Phalen test and neurophysiological studies were positive. Open carpal tunnel release showed an aberrant superficial branch of the radial artery with its accompanying veins running from radially to medially, almost parallel to the median nerve, ending at the superficial palmar arterial arch. The median nerve was decompressed without ligating the aberrant artery. At the last follow-up, 2 years after diagnosis and treatment the patient is asymptomatic.

  5. Bacterial colonization of colonic crypt mucous gel and disease activity in ulcerative colitis.

    LENUS (Irish Health Repository)

    Rowan, Fiachra

    2012-02-01

    OBJECTIVE: To optimize total bacterial 16S rRNA quantification in microdissected colonic crypts in healthy controls and patients with ulcerative colitis (UC) and to characterize the findings with disease activity. BACKGROUND: Microscopic and molecular techniques have recently converged to allow bacterial enumeration in remote anatomic locations [eg, crypt-associated mucous gel (CAMG)]. The aims of this study were to combine laser capture microdissection (LCM) and 16S rRNA-based quantitative polymerase chain reaction (qPCR) to determine total bacterial copy number in CAMG both in health and in UC and to characterize the findings with disease activity. METHODS: LCM was used to microdissect CAMG from colonic mucosal biopsies from controls (n = 20) and patients with acute (n = 10) or subacute (n = 10) UC. Pan-bacterial 16S rRNA copy number per millimeter square in samples from 6 locations across the large bowel was obtained by qPCR using Desulfovibrio desulfuricans as a reference strain. Copy numbers were correlated with the UC disease activity index (UCDAI) and the simple clinical colitis activity index (SCCAI). RESULTS: Bacterial colonization of CAMG was detectable in all groups. Copy numbers were significantly reduced in acute UC. In subacute colitis, there was a positive correlation between copy number and UCDAI and SCCAI in the ascending, transverse and sigmoid colon. CONCLUSIONS: This study describes a sensitive method of quantitatively assessing bacterial colonization of the colonic CAMG. A positive correlation was found between CAMG bacterial load and subacute disease activity in UC, whereas detectable bacterial load was reduced in acute UC.

  6. Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration.

    Science.gov (United States)

    Suga, Yasuyo; Takehana, Kenji

    2017-09-01

    S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b + TIM-4 + cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b + TIM-4 + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium.

    Science.gov (United States)

    Wang, Yuli; Gunasekara, Dulan B; Reed, Mark I; DiSalvo, Matthew; Bultman, Scott J; Sims, Christopher E; Magness, Scott T; Allbritton, Nancy L

    2017-06-01

    The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    , initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression. Overall, these results support the potential role of the DDR machinery as a barrier to gliomagenesis......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...... that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal...

  9. [Monochromatic aberration in accommodation. Dynamic wavefront analysis].

    Science.gov (United States)

    Fritzsch, M; Dawczynski, J; Jurkutat, S; Vollandt, R; Strobel, J

    2011-06-01

    Monochromatic aberrations may influence the visual acuity of the eye. They are not stable and can be affected by different factors. The subject of the following paper is the dynamic investigation of the changes in wavefront aberration with accommodation. Dynamic measurement of higher and lower order aberrations was performed with a WASCA Wavefront Analyzer (Carl-Zeiss-Meditec) and a specially constructed target device for aligning objects in far and near distances on 25 subjects aged from 15 to 27 years old. Wavefront aberrations showed some significant changes in accommodation. In addition to the characteristic sphere reaction accompanying miosis and changes in horizontal prism (Z(1) (1)) in the sense of a convergence movement of the eyeball also occurred. Furthermore defocus rose (Z(2) (0)) and astigmatism (Z(2) (-2)) changed. In higher-order aberrations a decrease in coma-like Zernike polynomials (Z(3) (-1), Z(3) (1)) was found. The most obvious change appeared in spherical aberration (Z(4) (0)) which increased and changed from positive to negative. In addition the secondary astigmatism (Z(4) (-2)) and quadrafoil (Z(4) (4)) rise also increased. The total root mean square (RMS), as well as the higher-order aberrations (RMS-HO) significantly increased in accommodation which is associated with a theoretical reduction of visual acuity. An analysis of the influence of pupil size on aberrations showed significant increases in defocus, spherical aberration, quadrafoil, RMS and RMS HO by increasing pupil diameter. By accommodation-associated miosis, the growing aberrations are partially compensated by focusing on near objects. Temporal analysis of the accommodation process with dynamic wavefront analysis revealed significant delays in pupil response and changing of prism in relation to the sphere reaction. In accommodation to near objects a discrete time ahead of third order aberrations in relation to the sphere response was found. Using dynamic wavefront measurement

  10. A two-dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro.

  11. Phenylbutazone induces expression of MBNL1 and suppresses formation of MBNL1-CUG RNA foci in a mouse model of myotonic dystrophy.

    Science.gov (United States)

    Chen, Guiying; Masuda, Akio; Konishi, Hiroyuki; Ohkawara, Bisei; Ito, Mikako; Kinoshita, Masanobu; Kiyama, Hiroshi; Matsuura, Tohru; Ohno, Kinji

    2016-04-29

    Myotonic dystrophy type 1 (DM1) is caused by abnormal expansion of CTG repeats in the 3' untranslated region of the DMPK gene. Expanded CTG repeats are transcribed into RNA and make an aggregate with a splicing regulator, MBNL1, in the nucleus, which is called the nuclear foci. The nuclear foci sequestrates and downregulates availability of MBNL1. Symptomatic treatments are available for DM1, but no rational therapy is available. In this study, we found that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone (PBZ), upregulated the expression of MBNL1 in C2C12 myoblasts as well as in the HSA(LR) mouse model for DM1. In the DM1 mice model, PBZ ameliorated aberrant splicing of Clcn1, Nfix, and Rpn2. PBZ increased expression of skeletal muscle chloride channel, decreased abnormal central nuclei of muscle fibers, and improved wheel-running activity in HSA(LR) mice. We found that the effect of PBZ was conferred by two distinct mechanisms. First, PBZ suppressed methylation of an enhancer region in Mbnl1 intron 1, and enhanced transcription of Mbnl1 mRNA. Second, PBZ attenuated binding of MBNL1 to abnormally expanded CUG repeats in cellulo and in vitro. Our studies suggest that PBZ is a potent therapeutic agent for DM1 that upregulates availability of MBNL1.

  12. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  13. Influence of anthropogenic transformation of Danube–Dniester interfluve on natural foci of tularaemia

    Directory of Open Access Journals (Sweden)

    I. T. Rusev

    2011-04-01

    Full Text Available The paper is devoted to the problem of occurrence of bacteria Francisella tularensis in steppe coastal zone of the Black Sea west part in the second half of XX century. The key factor decreasing the activity of tularaemia natural foci is anthropogenic influence. Resumed activity of natural foci appeared after implementation of big irrigation and drainage construction in former USSR – building of the Danube-Dniester-Dnepr irrigation system resulted in forming new environmental conditions as well as corridors for tularaemia distribution. The practical recommendation is to implement the eco-epizootological monitoring and to collect data for developing practical management of the natural foci of disease.

  14. I. The theory of aberrations of quadrupole focusing arrays. II. Ion optical design of high quality extracted synchrotron beams with application to the bevatron

    Energy Technology Data Exchange (ETDEWEB)

    Meads, Jr, Philip Francis [Univ. of California, Berkeley, CA (United States). Applied Science and Technology

    1963-05-15

    In Part One they formulate in a general way the problem of analyzing and evaluating the aberrations of quadrupole magnet beam systems, and of characterizing the shapes and other properties of the beam envelopes in the neighborhood of foci. They consider all aberrations, including those due to misalignments and faulty construction, through third order in small parameters, for quadrupole beam systems. One result of this study is the development of analytic and numerical techniques for treating these aberrations, yielding useful expressions for the comparison of the aberrations of different beam systems. A second result of this study is a comprehensive digital computer program that determines the magnitude and nature of the aberrations of such beam systems. The code, using linear programming techniques, will adjust the parameters of a beam system to obtain specified optical properties and to reduce the magnitude of aberrations that limit the performance of that system. They examine numerically, in detail, the aberrations of two typical beam systems. In Part Two, they examine the problem of extracting the proton beam from a synchrotron of 'H' type magnet construction. They describe the optical studies that resulted in the design of an external beam from the Bevatron that is optimized with respect to linear, dispersive, and aberration properties and that uses beam elements of conservative design. The design of the beam is the result of the collaboration of many people representing several disciplines. They describe the digital computer programs developed to carry out detailed orbit studies which were required because of the existence of large second order aberrations in the beam.

  15. Chromosomal aberrations in uranium and coal miners

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, G.; Arndt, D.; Kotschy-Lang, N.; Obe, G. [Robert Koch Inst., Berlin (Germany)

    2004-02-01

    Peripheral lymphocytes from 66 Wismut uranium miners (WUM) and 29 Ruhr coal miners (RGM) were cultured and analysed for structural chromosomal aberrations in Giemsa-stained M1 metaphases. Cytogenetic data from 23 male white-collar workers from public services were used as a historical control group. The frequencies of chromosomal aberrations and sister chromatid exchanges in WUM and RCM were quite similar. Compared with public services workers, WUM and RCM had significantly higher frequencies of chromosomal aberrations. It is concluded that chromosomal aberrations in WUM are not induced by radioactive particles inhaled during underground mining but as in RCM rather result from factors such as age, lifestyle, illnesses, medications and diagnostic irradiations.

  16. An aberrant precision account of autism

    National Research Council Canada - National Science Library

    Lawson, Rebecca P; Rees, Geraint; Friston, Karl J

    2014-01-01

    ... (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation-namely, predictive coding-many features of autistic perception can be attributed to aberrant precision...

  17. Aberration corrected Lorentz scanning transmission electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    McVitie, S., E-mail: stephen.mcvitie@glasgow.ac.uk; McGrouther, D.; McFadzean, S.; MacLaren, D.A.; O’Shea, K.J.; Benitez, M.J.

    2015-05-15

    We present results from an aberration corrected scanning transmission electron microscope which has been customised for high resolution quantitative Lorentz microscopy with the sample located in a magnetic field free or low field environment. We discuss the innovations in microscope instrumentation and additional hardware that underpin the imaging improvements in resolution and detection with a focus on developments in differential phase contrast microscopy. Examples from materials possessing nanometre scale variations in magnetisation illustrate the potential for aberration corrected Lorentz imaging as a tool to further our understanding of magnetism on this lengthscale. - Highlights: • Demonstration of nanometre scale resolution in magnetic field free environment using aberration correction in the scanning transmission electron microscope (STEM). • Implementation of differential phase contrast mode of Lorentz microscopy in aberration corrected STEM with improved sensitivity. • Quantitative imaging of magnetic induction of nanostructures in amorphous and cross-section samples.

  18. Epigenetic aberrations in myeloid malignancies (Review).

    Science.gov (United States)

    Takahashi, Shinichiro

    2013-09-01

    The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status. This review focuses on the current findings of aberrant epigenetic signatures by these newly described genetic alterations. Moreover, epigenetic aberrations resulting from transcription factor aberrations, such as mixed lineage leukemia (MLL) rearrangement, ecotropic viral integration site 1 (Evi1) overexpression, chromosomal translocations and the downregulation of PU.1 are also described.

  19. Concordance and discordance between PET images and foci of scalp EEG

    Energy Technology Data Exchange (ETDEWEB)

    Iinuma, Kazuie; Haginoya, Kazuhiro; Yanai, Kazuhiko (Tohoku Univ., Sendai (Japan). School of Medicine); Hatazawa, Jun; Ito, Masatoshi

    1989-09-01

    Epileptic foci were determined by scalp EEG and positron emission tomography (PET) with fluorine 18 in 22 children with partial epilepsy (PE, n=13) and Lennoxy-Gastaut syndrome (LGS, n=9). The patients ranged in age from 6 to 18 years. The pattern of hypometabolism was classified into the following 4 categories: non-focal, localized, hemispheric, and diffuse. In the group of PE patients, 11 showed a relative agreement between the EEG foci and region of a low cerebral metabolic rate for glucose (CMRglc) determined by PET. A decreased CMRglc was matched with the EEG foci in 4 patients with LGS. A tendency of a higher relationship between the EEG foci and PET images was significant in PE than LGS. (N.K.).

  20. Ground-penetrating radar investigation of St. Leonard's Crypt under the Wawel Cathedral (Cracow, Poland) - COST Action TU1208

    Science.gov (United States)

    Benedetto, Andrea; Pajewski, Lara; Dimitriadis, Klisthenis; Avlonitou, Pepi; Konstantakis, Yannis; Musiela, Małgorzata; Mitka, Bartosz; Lambot, Sébastien; Żakowska, Lidia

    2016-04-01

    The Wawel ensemble, including the Royal Castle, the Wawel Cathedral and other monuments, is perched on top of the Wawel hill immediately south of the Cracow Old Town, and is by far the most important collection of buildings in Poland. St. Leonard's Crypt is located under the Wawel Cathedral of St Stanislaus BM and St Wenceslaus M. It was built in the years 1090-1117 and was the western crypt of the pre-existing Romanesque Wawel Cathedral, so-called Hermanowska. Pope John Paul II said his first Mass on the altar of St. Leonard's Crypt on November 2, 1946, one day after his priestly ordination. The interior of the crypt is divided by eight columns into three naves with vaulted ceiling and ended with one apse. The tomb of Bishop Maurus, who died in 1118, is in the middle of the crypt under the floor; an inscription "+ MAVRVS EPC MCXVIII +" indicates the burial place and was made in 1938 after the completion of archaeological works which resulted in the discovery of this tomb. Moreover, the crypt hosts the tombs of six Polish kings and heroes: Michał Korybut Wiśniowiecki (King of the Polish-Lithuanian Commonwealth), Jan III Sobieski (King of the Polish-Lithuanian Commonwealth and Commander at the Battle of Vienna), Maria Kazimiera (Queen of the Polish-Lithuanian Commonwealth and consort to Jan III Sobieski), Józef Poniatowski (Prince of Poland and Marshal of France), Tadeusz Kościuszko (Polish general, revolutionary and a Brigadier General in the American Revolutionary War) and Władysław Sikorski (Prime Minister of the Polish Government in Exile and Commander-in-Chief of the Polish Armed Forces). The adjacent six crypts and corridors host the tombs of the other Polish kings, from Sigismund the Old to Augustus II the Strong, their families and several Polish heroes. In May 2015, the COST (European COoperation in Science and Technology) Action TU1208 "Civil engineering applications of Ground Penetrating Radar" organised and offered a Training School (TS) on the

  1. Localized air foci in the lower thorax in the patients with pneumothorax: Skip pneumothoraces

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takeshi, E-mail: higuchi@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Takahashi, Naoya, E-mail: nandtr@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Kiguchi, Takao, E-mail: takakig@gmail.com [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Shiotani, Motoi, E-mail: Shiotani14@gmail.com [Department of Radiology, Niigata Cancer Center Hospital, 2-15-3 Chuo-ku, Kawagishicho, Niigata 951-8566 (Japan); Maeda, Haruo, E-mail: h-maeda@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan)

    2013-08-15

    Purpose: To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Materials and methods: Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1–93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ{sup 2} test. All P values <0.05 were considered significant. Results: Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Conclusion: Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases.

  2. Impact of novel sorghum bran diets on DSS-induced colitis

    Science.gov (United States)

    Background. Repeated bouts of inflammation are known to promote colon cancer. We have reported that polyphenol-rich sorghum bran diets decrease formation of colon aberrant crypt foci, however, little is known regarding their effect during colonic inflammation. Objective. We hypothesized that sorgh...

  3. A sucrose-rich diet induces mutations in the rat colon

    DEFF Research Database (Denmark)

    Dragsted, Lars O.; Daneshvar, Bahram; Vogel, Ulla

    2002-01-01

    A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we hav...

  4. Pulse compressor with aberration correction

    Energy Technology Data Exchange (ETDEWEB)

    Mankos, Marian [Electron Optica, Inc., Palo Alto, CA (United States)

    2015-11-30

    In this SBIR project, Electron Optica, Inc. (EOI) is developing an electron mirror-based pulse compressor attachment to new and retrofitted dynamic transmission electron microscopes (DTEMs) and ultrafast electron diffraction (UED) cameras for improving the temporal resolution of these instruments from the characteristic range of a few picoseconds to a few nanoseconds and beyond, into the sub-100 femtosecond range. The improvement will enable electron microscopes and diffraction cameras to better resolve the dynamics of reactions in the areas of solid state physics, chemistry, and biology. EOI’s pulse compressor technology utilizes the combination of electron mirror optics and a magnetic beam separator to compress the electron pulse. The design exploits the symmetry inherent in reversing the electron trajectory in the mirror in order to compress the temporally broadened beam. This system also simultaneously corrects the chromatic and spherical aberration of the objective lens for improved spatial resolution. This correction will be found valuable as the source size is reduced with laser-triggered point source emitters. With such emitters, it might be possible to significantly reduce the illuminated area and carry out ultrafast diffraction experiments from small regions of the sample, e.g. from individual grains or nanoparticles. During phase I, EOI drafted a set of candidate pulse compressor architectures and evaluated the trade-offs between temporal resolution and electron bunch size to achieve the optimum design for two particular applications with market potential: increasing the temporal and spatial resolution of UEDs, and increasing the temporal and spatial resolution of DTEMs. Specialized software packages that have been developed by MEBS, Ltd. were used to calculate the electron optical properties of the key pulse compressor components: namely, the magnetic prism, the electron mirror, and the electron lenses. In the final step, these results were folded

  5. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  6. Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Chad M.; Wolf, Jeffrey C.; Elbekai, Reem H.; Paranjpe, Madhav G.; Seiter, Jennifer M.; Chappell, Mark A.; Tappero, Ryan V.; Suh, Mina; Proctor, Deborah M.; Bichteler, Anne; Haws, Laurie C.; Harris, Mark A.

    2015-08-01

    Lifetime exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal damage and an increase in duodenal tumors in B6C3F1 mice. To assess whether these tumors could be the result of a direct mutagenic or genotoxic mode of action, we conducted a GLP-compliant 7-day drinking water study to assess crypt health along the entire length of the duodenum. Mice were exposed to water (vehicle control), 1.4, 21, or 180 ppm Cr(VI) via drinking water for 7 consecutive days. Crypt enterocytes in Swiss roll sections were scored as normal, mitotic, apoptotic, karyorrhectic, or as having micronuclei. A single oral gavage of 50 mg/kg cyclophosphamide served as a positive control for micronucleus induction. Exposure to 21 and 180 ppm Cr(VI) significantly increased the number of crypt enterocytes. Micronuclei and γ-H2AX immunostaining were not elevated in the crypts of Cr(VI)-treated mice. In contrast, treatment with cyclophosphamide significantly increased numbers of crypt micronuclei and qualitatively increased γ-H2AX immunostaining. Synchrotron-based X-ray fluorescence (XRF) microscopy revealed the presence of strong Cr fluorescence in duodenal villi, but negligible Cr fluorescence in the crypt compartment. Together, these data indicate that Cr(VI) does not adversely effect the crypt compartment where intestinal stem cells reside, and provide additional evidence that the mode of action for Cr(VI)-induced intestinal cancer in B6C3F1 mice involves chronic villous wounding resulting in compensatory crypt enterocyte hyperplasia.

  7. Study of ocular aberrations with age.

    Science.gov (United States)

    Athaide, Helaine Vinche Zampar; Campos, Mauro; Costa, Charles

    2009-01-01

    Aging has various effects on visual system. Vision deteriorate, contrast sensitivity decreases and ocular aberrations apparently make the optical quality worse across the years. To prospective evaluate ocular aberrations along the ages. Three hundred and fifteen patients were examined, 155 were male (39.36%) and 160 were female (60.63%). Ages ranged from 5 to 64 year-old, the study was performed from February to November, 2004. Patients were divided into 4 age-groups according to IBGE (Instituto Brasileiro de Geografia e Estatística) classification: 68 patients from 5 to 14 year-old, 55 patients from 15 to 24 year-old, 116 from 25 to 44 year-old and 76 from 45 to 67 year-old. All patients had the following characteristics: best corrected visual acuity > 20/25, emmetropia or spherical equivalent < 3.50 SD, refractive astigmatism < 1.75 CD on cycloplegic refraction, normal ophthalmologic exam and no previous ocular surgeries. This protocol was approved by Federal University of São Paulo Institutional Review Board. Total optical aberrations were measured by H-S sensor LadarWave Custom Cornea Wavefront System (Alcon Laboratories Inc, Orlando, FLA, USA) and were statistically analysed. Corneal aberrations were calculated using CT-View software Version 6.89 (Sarver and Associates, Celebration, FL, USA). Lens aberrations were calculated by subtraction. High-order (0.32 e 0.48 microm) and ocular spherical aberrations (0.02 e 0.26 microm) increased respectively in child and middle age groups. High order (0.27 microm) and corneal spherical aberrations (0.05 microm) did not show changes with age. Lens showed a statistically significant spherical aberration increase (from -0.02 to 0.22 microm). Vertical (from 0.10 to -0.07 microm) and horizontal coma (from 0.01 to -0.12 microm) presented progressively negative values with aging. High-order and spherical aberrations increased with age due to lens contribution. The cornea did not affect significantly changes observed on ocular

  8. Influence of cis-diamminedichloroplatinum (II) on mouse duodenal crypt stem cell survival after multifraction X ray treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dewit, L.; Begg, A.C.; Koehler, Y.S.; Stewart, F.A.; Bartelink, H.

    1985-10-01

    The mechanism of interaction of cis-platinum and X rays was investigated in mouse duodenal crypts using the microcolony assay. Mice were exposed to 1, 2, 5, 10, or 15 fractions of X rays, either alone or preceded by a single i.p. injection of cis-platinum, 8 mg/kg, one-half hour before the first fraction. In all fractionation regimens, cisplatinum caused a shift of the X ray survival curve for crypt cells towards lower doses. The vertical distances between the survival curves after X rays and those in combination with cis-platinum were about the same. After cis-platinum treatment alone, a crypt cell survival curve was established in the high dose range. The estimated cell kill by 8 mg/kg of cis-platinum, obtained by extrapolation of this curve, was 1 log10 cell number. These data imply independent cell killing mechanisms for cis-platinum and X rays. However, even after correction for cell kill by the drug, cis-platinum tended to inhibit slightly sublethal damage repair after X rays. This was supported by linear quadratic analyses, in which the alpha/beta value after combined treatment was found to be slightly higher than after X rays alone.

  9. Mammalian Target of Rapamycin Signaling Pathway Changes with Intestinal Epithelial Cells Renewal Along Crypt-Villus Axis

    Directory of Open Access Journals (Sweden)

    Huansheng Yang

    2016-07-01

    Full Text Available Background/Aims: Understanding the mechanism that involves in regulating epithelial cells renewal is the fundamental of regulating intestinal mucosa development and functions and related diseases. The mechanistic target of rapamycin (mTOR signaling pathway involves in controlling various major processes by integrating intracellular and extracellular cues. The present experiment was conducted to test the correlation between the mTOR signaling pathway and intestinal epithelial cells renewal along crypt-villus axis (CVA. Methods: Intestinal epithelial cells were sequentially isolated from the jejunum of piglets along CVA, and the amount or phosphorylation level of proteins involved in cell cycle, mTOR signaling pathway, gene expression, and the antioxidant capacity in the isolated cells were measured. Results: The results showed that the amount of proteins involved in cell cycle decreased from crypt to villus tip. The amount or phosphorylation level of proteins related to mTOR signaling pathway in intestinal epithelial cells mainly decreased during maturation along CVA. The amount of proteins involved in gene expression and the antioxidant capacity also decreased from crypt to the top of villi. Conclusions: These results indicate that the mTOR signaling pathway may be involved in regulating the intestinal epithelial cells renewal along CVA and it may partly through affecting the antioxidant capacity and gene expression of intestinal epithelial cells. Further histological verification is needed to confirm the results of the present experiments.

  10. Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

    Science.gov (United States)

    Woldemeskel, M W; Saliki, J T; Blas-Machado, U; Whittington, L

    2013-11-01

    The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

  11. Crypt stem cells as the cells-of-origin of intestinal cancer.

    Science.gov (United States)

    Barker, Nick; Ridgway, Rachel A; van Es, Johan H; van de Wetering, Marc; Begthel, Harry; van den Born, Maaike; Danenberg, Esther; Clarke, Alan R; Sansom, Owen J; Clevers, Hans

    2009-01-29

    Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived intestinal stem cells. Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5(+) cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.

  12. Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.

    Directory of Open Access Journals (Sweden)

    Lise Michel

    Full Text Available Myotonic dystrophy type 1 (DM1 is caused by an unstable expanded CTG repeat located within the DMPK gene 3'UTR. The nature, severity and age at onset of DM1 symptoms are very variable in patients. Different forms of the disease are described, among which the congenital form (CDM is the most severe. Molecular mechanisms of DM1 are well characterized for the adult form and involve accumulation of mutant DMPK RNA forming foci in the nucleus. These RNA foci sequester proteins from the MBNL family and deregulate CELF proteins. These proteins are involved in many cellular mechanisms such as alternative splicing, transcriptional, translational and post-translational regulation miRNA regulation as well as mRNA polyadenylation and localization. All these mechanisms can be impaired in DM1 because of the deregulation of CELF and MBNL functions. The mechanisms involved in CDM are not clearly described. In order to get insight into the mechanisms underlying CDM, we investigated if expanded RNA nuclear foci, one of the molecular hallmarks of DM1, could be detected in human DM1 fetal tissues, as well as in embryonic and neonatal tissues from transgenic mice carrying the human DMPK gene with an expanded CTG repeat. We observed very abundant RNA foci formed by sense DMPK RNA and, to a lesser extent, antisense DMPK RNA foci. Sense DMPK RNA foci clearly co-localized with MBNL1 and MBNL2 proteins. In addition, we studied DMPK sense and antisense expression during development in the transgenic mice. We found that DMPK sense and antisense transcripts are expressed from embryonic and fetal stages in heart, muscle and brain and are regulated during development. These results suggest that mechanisms underlying DM1 and CDM involved common players including toxic expanded RNA forming numerous nuclear foci at early stages during development.

  13. Localized air foci in the lower thorax in the patients with pneumothorax: skip pneumothoraces.

    Science.gov (United States)

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-08-01

    To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1-93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ(2) test. All P values thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Calculation of aberration coefficients by ray tracing.

    Science.gov (United States)

    Oral, M; Lencová, B

    2009-10-01

    In this paper we present an approach for the calculation of aberration coefficients using accurate ray tracing. For a given optical system, intersections of a large number of trajectories with a given plane are computed. In the Gaussian image plane the imaging with the selected optical system can be described by paraxial and aberration coefficients (geometric and chromatic) that can be calculated by least-squares fitting of the analytical model on the computed trajectory positions. An advantage of such a way of computing the aberration coefficients is that, in comparison with the aberration integrals and the differential algebra method, it is relatively easy to use and its complexity stays almost constant with the growing complexity of the optical system. This paper shows a tested procedure for choosing proper initial conditions and computing the coefficients of the fifth-order geometrical and third-order, first-degree chromatic aberrations by ray tracing on an example of a weak electrostatic lens. The results are compared with the values for the same lens from a paper Liu [Ultramicroscopy 106 (2006) 220-232].

  15. Describing ocular aberrations with wavefront vergence maps.

    Science.gov (United States)

    Nam, Jayoung; Thibos, Larry N; Iskander, D Robert

    2009-05-01

    A common optometric problem is to specify the eye's ocular aberrations in terms of Zernike coefficients and to reduce that specification to a prescription for the optimum sphero-cylindrical correcting lens. The typical approach is first to reconstruct wavefront phase errors from measurements of wavefront slopes obtained by a wavefront aberrometer. This paper applies a new method to this clinical problem that does not require wavefront reconstruction. Instead, we base our analysis of axial wavefront vergence as inferred directly from wavefront slopes. The result is a wavefront vergence map that is similar to the axial power maps in corneal topography and hence has a potential to be favoured by clinicians. We use our new set of orthogonal Zernike slope polynomials to systematically analyse details of the vergence map analogous to Zernike analysis of wavefront maps. The result is a vector of slope coefficients that describe fundamental aberration components. Three different methods for reducing slope coefficients to a spherocylindrical prescription in power vector forms are compared and contrasted. When the original wavefront contains only second order aberrations, the vergence map is a function of meridian only and the power vectors from all three methods are identical. The differences in the methods begin to appear as we include higher order aberrations, in which case the wavefront vergence map is more complicated. Finally, we discuss the advantages and limitations of vergence map representation of ocular aberrations.

  16. Effects of chalazion excision on ocular aberrations.

    Science.gov (United States)

    Sabermoghaddam, Ali A; Zarei-Ghanavati, Siamak; Abrishami, Mojtaba

    2013-06-01

    The goal of this study was to compare higher-order aberrations before and after upper lid chalazion excision. Fourteen eyes from 12 patients (8 females, mean age: 28.7 ± 2.7 years) with upper lid chalazion were enrolled in this prospective interventional case series. Chalazia were excised by standard transconjunctival vertical incision. Ocular aberrations were evaluated by aberrometry (ZyWave) before and 2 months after chalazion excision. Root mean square of total higher-order aberrations decreased from 0.67 ± 0.12 to 0.43 ± 0.15 μm (P = 0.012) after excision. The root mean square of Zernike orders in the vertical and horizontal trefoil and horizontal coma were decreased after excision. Orbscan IIz tomography showed a statistically significant decrease in 5 mm zone irregularity (P = 0.027) and an increase in minimum simulated keratometry after surgery (P = 0.046). Chalazion increases higher-order aberrations, as measured by the Hartmann-Shack aberrometer, which could affect the preoperative evaluation and results of refractive surgery, especially wavefront-guided approaches. Chalazion excision could reduce ocular aberrations and is recommended before refractive surgeries.

  17. A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments.

    Science.gov (United States)

    Bravo, Rafael; Axelrod, David E

    2013-11-18

    Normal colon crypts consist of stem cells, proliferating cells, and differentiated cells. Abnormal rates of proliferation and differentiation can initiate colon cancer. We have measured the variation in the number of each of these cell types in multiple crypts in normal human biopsy specimens. This has provided the opportunity to produce a calibrated computational model that simulates cell dynamics in normal human crypts, and by changing model parameter values, to simulate the initiation and treatment of colon cancer. An agent-based model of stochastic cell dynamics in human colon crypts was developed in the multi-platform open-source application NetLogo. It was assumed that each cell's probability of proliferation and probability of death is determined by its position in two gradients along the crypt axis, a divide gradient and in a die gradient. A cell's type is not intrinsic, but rather is determined by its position in the divide gradient. Cell types are dynamic, plastic, and inter-convertible. Parameter values were determined for the shape of each of the gradients, and for a cell's response to the gradients. This was done by parameter sweeps that indicated the values that reproduced the measured number and variation of each cell type, and produced quasi-stationary stochastic dynamics. The behavior of the model was verified by its ability to reproduce the experimentally observed monocolonal conversion by neutral drift, the formation of adenomas resulting from mutations either at the top or bottom of the crypt, and by the robust ability of crypts to recover from perturbation by cytotoxic agents. One use of the virtual crypt model was demonstrated by evaluating different cancer chemotherapy and radiation scheduling protocols. A virtual crypt has been developed that simulates the quasi-stationary stochastic cell dynamics of normal human colon crypts. It is unique in that it has been calibrated with measurements of human biopsy specimens, and it can simulate the

  18. Refractive surgery, optical aberrations, and visual performance.

    Science.gov (United States)

    Applegate, R A; Howland, H C

    1997-01-01

    Visual optics is taking on new clinical significance. Given that current refractive procedures can and do induce large amounts of higher order ocular aberration that often affects the patient's daily visual function and quality of life, we can no longer relegate the considerations of ocular aberrations to academic discussions. Instead, we need to move toward minimizing (not increasing) the eye's aberrations at the same time we are correcting the eye's spherical and cylindrical refractive error. These are exciting times in refractive surgery, which need to be tempered by the fact that after all the research, clinical, and marketing dust settles, the level to which we improve the quality of the retinal image will be guided by the trade-off between cost and the improvement in the quality of life that refractive surgery offers.

  19. An aberrant precision account of autism.

    Directory of Open Access Journals (Sweden)

    Rebecca P Lawson

    2014-05-01

    Full Text Available Autism is a neurodevelopmental disorder characterised by problems with social-communication, restricted interests and repetitive behaviour. A recent and controversial article presented a compelling normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012. In response, we suggested that when Bayesian interference is grounded in its neural instantiation – namely, predictive coding – many features of autistic perception can be attributed to aberrant precision (or beliefs about precision within the context of hierarchical message passing in the brain (Friston et al., 2013. Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings – that speak directly or indirectly to neurobiological mechanisms – are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs.

  20. Optical aberrations in professional baseball players.

    Science.gov (United States)

    Kirschen, David G; Laby, Daniel M; Kirschen, Matthew P; Applegate, Raymond; Thibos, Larry N

    2010-03-01

    To determine the presence, type, and size of optical higher-order aberrations (HOAs) in professional athletes with superior visual acuity and to compare them with those in an age-matched population of nonathletes. Vero Beach and Fort Myers, Florida, USA. Players from 2 professional baseball teams were studied. Each player's optical aberrations were measured with a naturally dilated 4.0 mm pupil using a Z-Wave aberrometer and a LADARWave aberrometer. One hundred sixty-two players (316 eyes) were evaluated. The HOAs were less than 0.026 mum in all cases. Spherical aberration C(4,0) was the largest aberration with both aberrometers. There were small but statistically significant differences between the aberrometers in mean values for trefoil C(3,3) and C(3,-3) and secondary astigmatism C(4,2). Although statistically significant, the differences were clinically insignificant, being similar at approximately 0.031 diopter (D) of spherical power. A statistically significant difference was found between the professional baseball players and the control population in trefoil C(3,-3). These differences were clinically insignificant, similar to 0.071 D of spherical power. Professional baseball players have small higher-order optical aberrations when tested with naturally dilated pupils. No clinically significant differences were found between the 2 aberrometers. Statistically significant differences in trefoil were found between the players and the control population; however, the difference was clinically insignificant. It seems as though the visual system of professional baseball players is limited by lower-order aberrations and that the smaller HOAs do not enhance visual function over that in a control population. Copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  1. A comprehensive statistical classifier of foci in the cell transformation assay for carcinogenicity testing.

    Science.gov (United States)

    Callegaro, Giulia; Malkoc, Kasja; Corvi, Raffaella; Urani, Chiara; Stefanini, Federico M

    2017-12-01

    The identification of the carcinogenic risk of chemicals is currently mainly based on animal studies. The in vitro Cell Transformation Assays (CTAs) are a promising alternative to be considered in an integrated approach. CTAs measure the induction of foci of transformed cells. CTAs model key stages of the in vivo neoplastic process and are able to detect both genotoxic and some non-genotoxic compounds, being the only in vitro method able to deal with the latter. Despite their favorable features, CTAs can be further improved, especially reducing the possible subjectivity arising from the last phase of the protocol, namely visual scoring of foci using coded morphological features. By taking advantage of digital image analysis, the aim of our work is to translate morphological features into statistical descriptors of foci images, and to use them to mimic the classification performances of the visual scorer to discriminate between transformed and non-transformed foci. Here we present a classifier based on five descriptors trained on a dataset of 1364 foci, obtained with different compounds and concentrations. Our classifier showed accuracy, sensitivity and specificity equal to 0.77 and an area under the curve (AUC) of 0.84. The presented classifier outperforms a previously published model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Imaging foci of epileptic discharges from simultaneous EEG and fMRI using the canonical HRF.

    Science.gov (United States)

    Luo, Cheng; Yao, Zhiping; Li, Qifu; Lei, Xu; Zhou, Dong; Qin, Yun; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Yao, Dezhong

    2010-10-01

    Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is considered as a powerful and non-invasive method that allows definition of the irritative zone. However, the complex interictal epileptic discharge (IED) may be present in some patients, and sometimes no active foci can be localized using General Linear Model (GLM) which is a widely adopted tool in EEG-fMRI study. The purpose of this study is to develop a new scheme to improve the detectability and localize the canonical HRF localizable foci. Various IEDs are classified using a combination of an independent component analysis (ICA) and a temporal correlation analysis between the independent components and the raw EEG channel; and the classified IEDs are then separately used for foci localization. This scheme is tested by ten patients with variable IEDs, including two patients whose activity could not be identified by common method. Applying this scheme to the two patients, some foci consistent with electroclinical data were localized. When it was applied to the remaining eight patients with positive results using common method, 2-4 types of IEDs were classified, and the activity could be identified from at least one type of IED. The results were similar to that received from common method. These results indicate that the proposed scheme could enhance the imaging of the localizable foci by isolating its IEDs. This scheme is potentially a useful tool for epilepsy clinic. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    CS Barbosa

    2004-08-01

    Full Text Available Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS, and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

  4. Determining the control networks regulating stem cell lineages in colonic crypts.

    Science.gov (United States)

    Yang, Jienian; Axelrod, David E; Komarova, Natalia L

    2017-09-21

    The question of stem cell control is at the center of our understanding of tissue functioning, both in healthy and cancerous conditions. It is well accepted that cellular fate decisions (such as divisions, differentiation, apoptosis) are orchestrated by a network of regulatory signals emitted by different cell populations in the lineage and the surrounding tissue. The exact regulatory network that governs stem cell lineages in a given tissue is usually unknown. Here we propose an algorithm to identify a set of candidate control networks that are compatible with (a) measured means and variances of cell populations in different compartments, (b) qualitative information on cell population dynamics, such as the existence of local controls and oscillatory reaction of the system to population size perturbations, and (c) statistics of correlations between cell numbers in different compartments. Using the example of human colon crypts, where lineages are comprised of stem cells, transit amplifying cells, and differentiated cells, we start with a theoretically known set of 32 smallest control networks compatible with tissue stability. Utilizing near-equilibrium stochastic calculus of stem cells developed earlier, we apply a series of tests, where we compare the networks' expected behavior with the observations. This allows us to exclude most of the networks, until only three, very similar, candidate networks remain, which are most compatible with the measurements. This work demonstrates how theoretical analysis of control networks combined with only static biological data can shed light onto the inner workings of stem cell lineages, in the absence of direct experimental assessment of regulatory signaling mechanisms. The resulting candidate networks are dominated by negative control loops and possess the following properties: (1) stem cell division decisions are negatively controlled by the stem cell population, (2) stem cell differentiation decisions are negatively

  5. A Review of Impact of Bam Earthquake on Cutaneous Leishmaniasis and Status: Epidemic of Old Foci, Emergence of New Foci and Changes in Features of the Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Aflatoonian

    2016-01-01

    Full Text Available Background: Global findings indicate that incidence rate of cutaneous leishmaniasis (CL has significantly in­creased during the past decade, as documented in many countries. This review was aimed to evaluate the trend of CL cases in terms of demographic and clinical characteristics during a decade after the earthquake (2003–2012 com­pared to the corresponding period before the earthquake in Bam (1993–2003.Methods: Direct smear preparations along with different intrinsic methods were used for detection and identification of the causative agents.Results: Overall, 20999 cases of CL have occurred during the last 20 years (1993–2012, 6731 cases before and 14268 cases after the earthquake (P< 0.001.Conclusions: Following a major earthquake, several risk factors could activate epidemics of cutaneous leishmaniasis in old foci and induce emerging foci in new areas.

  6. A Review of Impact of Bam Earthquake on Cutaneous Leishmaniasis and Status: Epidemic of Old Foci, Emergence of New Foci and Changes in Features of the Disease

    Science.gov (United States)

    Aflatoonian, Mohammad Reza; Sharifi, Iraj; Aflatoonian, Bahnaz; Shirzadi, Mohammad Reza; Gouya, Mohammad Mahdi; Kermanizadeh, Alireza

    2016-01-01

    Background: Global findings indicate that incidence rate of cutaneous leishmaniasis (CL) has significantly increased during the past decade, as documented in many countries. This review was aimed to evaluate the trend of CL cases in terms of demographic and clinical characteristics during a decade after the earthquake (2003–2012) compared to the corresponding period before the earthquake in Bam (1993–2003). Methods: Direct smear preparations along with different intrinsic methods were used for detection and identification of the causative agents. Results: Overall, 20999 cases of CL have occurred during the last 20 years (1993–2012), 6731 cases before and 14268 cases after the earthquake (P< 0.001). Conclusions: Following a major earthquake, several risk factors could activate epidemics of cutaneous leishmaniasis in old foci and induce emerging foci in new areas. PMID:27308286

  7. Identification of Chinese plague foci from long-term epidemiological data

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  8. Quantitative image analysis of gamma-H2AX foci induced by ionizing radiation applying open source programs.

    Science.gov (United States)

    González, Jorge Ernesto; Lee, Manual; Barquinero, Joan Francesc; Valente, Marco; Roch-Lefèvre, Sandrine; García, Omar

    2012-04-01

    To test a CellProfiler pipeline for automated counting and characterization of gamma-H2AX foci in color images of human cultured cells. A431 cells were irradiated and stained for gamma-H2AX foci detection. Sets of color images were analyzed visually, and findings were compared with those using FociCounter and CellProfiler software. The CellProfiler pipeline includes some proprieties not present in FociCounter, such as the automatic detection of nuclei, the detection of touching nuclei and the rejection of nuclei that touch the border of the image. The time required for manual operation is associated with the number of images analyzed visually or by FociCounter but not for the CellProfiler program. CellProfiler reduced manual operation time and is about 4 times faster than semiautomatic detection using FociCounter and 10 times faster than visual counting. We conclude that CellProfiler and FociCounter are reliable tools for measuring gamma-H2AX foci. However, CellProfiler overcomes the limitations of the FociCounter program and is able to detect nuclei automatically, saving considerable manual operation.

  9. The correction of electron lens aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Hawkes, P.W., E-mail: peter.hawkes@cemes.fr

    2015-09-15

    The progress of electron lens aberration correction from about 1990 onwards is chronicled. Reasonably complete lists of publications on this and related topics are appended. A present for Max Haider and Ondrej Krivanek in the year of their 65th birthdays. By a happy coincidence, this review was completed in the year that both Max Haider and Ondrej Krivanek reached the age of 65. It is a pleasure to dedicate it to the two leading actors in the saga of aberration corrector design and construction. They would both wish to associate their colleagues with such a tribute but it is the names of Haider and Krivanek (not forgetting Joachim Zach) that will remain in the annals of electron optics, next to that of Harald Rose. I am proud to know that both regard me as a friend as well as a colleague. - Highlights: • Geometrical aberration correction. • Chromatic aberration correction. • 50 pm resolution. • High-resolution electron energy-loss spectroscopy. • Extensive bibliographies.

  10. Chromosomal aberrations induced by Markhamia tomentosa (Benth ...

    African Journals Online (AJOL)

    Markhamia tomentosa (Benth.) K. Schum. Ex Engl. (Bignoniaceae) is used traditionally in the treatment of pain, oedema, pulmonary troubles and cancer. The genotoxic and cytotoxic effects of the ethanolic extract of the leaves of M. tomentosa was investigated using the Allium cepa root chromosomal aberration assay.

  11. Anti-forensics of chromatic aberration

    Science.gov (United States)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  12. Dose-dependent emergence of preneoplastic foci in rat livers after exposure to 2-nitropropane.

    Science.gov (United States)

    Denk, B; Filser, J G; Deml, E; Kessler, W; Shen, J; Oesterle, D

    1990-01-01

    Male and female Sprague-Dawley rats, 4-6 days old were exposed for 3 weeks (6 h/day, 5 days/week) to 2-nitropropane vapours of 0, 25, 40, 50, 80 and 125 ppm. One week later polychlorinated biphenyls (Clophen A50, 10 mg/kg body weight) were administered for promotion twice a week for 8 weeks. Thirteen weeks after starting the experiments the logarithms of the numbers of preneoplastic liver foci deficient in adenosine-5'-triphosphatase were found to be linearly related to the exposure concentrations of 2-nitropropane. Male rats exhibited an approximately four times lower foci incidence than females.

  13. Transforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling.

    Science.gov (United States)

    Booth, D; Haley, J D; Bruskin, A M; Potten, C S

    2000-04-01

    Damage to the normal replacing tissues of the body, specifically the gastro-intestinal tract, limits the treatment and hence, cure rate of cancer patients. Here, we investigate the possibility that the sensitivity of the gastro-intestinal tract can be manipulated by transforming growth factor beta3 (TGF-beta3), making it more resistant to radiation in a murine model. The effects of TGF-beta3 were assessed using the crypt microcolony assay, a test of crypt stem-cell functional competence, in animal survival studies examining diarrhoea severity, labelling index and crypt size. Prior treatment with TGF-beta3 can result in a 3- to 4-fold increase (protection factor, PF) in surviving crypts, whilst longer exposure can raise the PF to almost 12. Protection of intestinal clonogenic stem cells results in marked protection of survival with a corresponding reduction in the duration and level of diarrhoea and ultimate restoration of normal histology in surviving mice. Inhibition of proliferation can be demonstrated when sufficient TGF-beta3 exposure is studied. Crypt size is also reduced. In conclusion, TGF-beta3 protects small intestinal clonogenic stem cells from radiation damage, reducing diarrhoea and animal mortality. The mode of action is believed to be specific inhibition of stem-cell proliferation.

  14. Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells.

    Science.gov (United States)

    Vincent, Audrey; Kazmierczak, Catherine; Duchêne, Belinda; Jonckheere, Nicolas; Leteurtre, Emmanuelle; Van Seuningen, Isabelle

    2015-01-01

    The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, methylation-specific PCR and micro-chromatin immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts and (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms. Copyright © 2015. Published by Elsevier B.V.

  15. Cryosectioning the intestinal crypt-villus axis: An ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells

    Directory of Open Access Journals (Sweden)

    Audrey Vincent

    2015-01-01

    Full Text Available The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, methylation-specific PCR and micro-chromatin immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i expression of intestinal stem cell markers (Lgr5, Ascl2 exclusively in the crypt is associated with active histone marks, (ii promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2 harbour a bivalent chromatin pattern in the crypts and (iii expression of differentiation markers (Muc2, Sox9 along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms.

  16. Higher-order aberrations and anisometropia.

    Science.gov (United States)

    Hartwig, Andreas; Atchison, David A; Radhakrishnan, Hema

    2013-01-01

    Myopia incidence is increasing around the world. Myopization is considered to be caused by a variety of factors. One consideration is whether higher-order aberrations (HOA) influence myopization. More knowledge of optics in anisometropic eyes might give further insight into the development of refractive error. To analyze the possible influence of HOA on refractive error development, we compared HOA between anisometropes and isometropes. We analyzed HOA up to the 4th order for both eyes of 20 anisometropes (mean age: 43 ± 17 years) and 20 isometropes (mean age: 33 ± 17 years). HOA were measured with the Shack-Hartman i.Profiler (Carl Zeiss, Germany) and were recalculated for a 4 mm pupil. Mean spherical equivalent (MSE) was based on the subjective refraction. Anisometropia was defined as ≥1 D interocular difference in MSE. The mean absolute differences between right and left eyes in spherical equivalent were 0.28 ± 0.21 D in the isometropic group and 2.81 ± 2.04 D in the anisometropic group. Interocular differences in HOA were compared with the interocular difference in MSE using correlations. For isometropes oblique trefoil, vertical coma, horizontal coma and spherical aberration showed significant correlations between the two eyes. In anisometropes, all analyzed higher-order aberrations correlated significantly between the two eyes except oblique secondary astigmatism and secondary astigmatism. When analyzing anisometropes and isometropes separately, no significant correlations were found between interocular differences of higher-order aberrations and MSE. For isometropes and anisometropes combined, tetrafoil correlated significantly with MSE in left eyes. The present study could not show that interocular differences of higher-order aberrations increase with increasing interocular difference in MSE.

  17. Functional morphology, biology and sexual strategy of the circumboreal, adventitious crypt-building, Crenella decussata (Bivalvia: Mytiloidea: Crenellidae)

    DEFF Research Database (Denmark)

    Morton, Brian; Dinesen, Grete E.; Ockelmann, Kurt W.

    2016-01-01

    to the prodissoconch stage. Subsequently, these larvae are transferred to the exhalant tube of the crypt wherein they attach by a single fine byssal thread and are further brooded until the crawl-away juvenile stage is attained. Experimental studies of larval behaviour suggest that parental pheromones sustain...... the female/offspring bond. Newly hatched individuals responded to parental exhalant water by actively attaching themselves using a byssal thread. This response persisted for 28 days, but not after 55 days when, we suggest, the pheromonal response ceases and offspring are developed sufficiently to take up...

  18. Theoretical investigation of aberrations upon ametropic human eyes

    Science.gov (United States)

    Tan, Bo; Chen, Ying-Ling; Lewis, J. W. L.; Baker, Kevin

    2003-11-01

    The human eye aberrations are important for visual acuity and ophthalmic diagnostics and surgical procedures. Reported monochromatic aberration data of the normal 20/20 human eyes are scarce. There exist even fewer reports of the relation between ametropic conditions and aberrations. We theoretically investigate the monochromatic and chromatic aberrations of human eyes for refractive errors of -10 to +10 diopters. Schematic human eye models are employed using optical design software for axial, index, and refractive types of ametropia.

  19. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

    2011-03-04

    Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

  20. Impact of Physico-Chemical Factors of Contaminated Foci on the ...

    African Journals Online (AJOL)

    Physio-chemical analysis of 200 soil samples collected from contaminated foci was investigated in six communities of Abua, Niger Delta Nigeria. The Jackson's method was used in the chemical analysis of contaminated soils while Cobb's decanting and sieving method was used in the extraction of geohelminths. The data ...

  1. Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa.

    Science.gov (United States)

    Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

    2014-01-01

    The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch's membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, Pretinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa.

  2. Evidence of dental screening for oral foci of infection in oncology patients

    NARCIS (Netherlands)

    Schuurhuis, Jennifer Marleen

    2016-01-01

    Pre-treatment dental screening of, amongst others, head-and-neck-cancer and hematology patients aims to identify and eliminate oral foci of infection to prevent oral problems during or post-treatment. The efficacy of dental screening in these patients is yet not evidence based. In particular in high

  3. Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

    Science.gov (United States)

    Jiruska, Premysl; Proks, Jan; Otáhal, Jakub; Mares, Pavel

    2007-10-01

    Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.

  4. Piscine orthoreovirus (PRV) in red and melanised foci in white muscle of Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Bjørgen, Håvard; Wessel, Øystein; Fjelldal, Per Gunnar; Hansen, Tom; Sveier, Harald; Sæbø, Håkon Rydland; Enger, Katrine Bones; Monsen, Eirik; Kvellestad, Agnar; Rimstad, Espen; Koppang, Erling Olaf

    2015-09-08

    Melanised focal changes (black spots) are common findings in the white skeletal muscle of seawater-farmed Atlantic salmon (Salmo salar). Fillets with melanised focal changes are considered as lower quality and cause large economic losses. It has been suggested that red focal changes (red spots) precede the melanised focal changes. In the present work, we examined different populations of captive and wild salmon for the occurrence of both types of changes, which were investigated for the presence of different viruses by immunohistochemistry and RT-qPCR. The occurrence of red or melanised foci varied significantly between the populations, from none in wild fish control group, low prevalence of small foci in fish kept in in-house tanks, to high prevalence of large foci in farm-raised salmon. Large amounts of Piscine orthoreovirus (PRV) antigen were detected in all foci. No other viruses were detected. Red focal changes contained significantly higher levels of PRV RNA than apparently non-affected areas in white muscle of the same individuals. Some changes displayed a transient form between a red and melanised pathotype, indicating a progression from an acute to a chronic manifestation. We conclude that PRV is associated with the focal pathological changes in the white muscle of farmed Atlantic salmon and is a premise for the development of focal melanised changes.

  5. S phase progression in human cells is dictated by the genetic continuity of DNA foci.

    Directory of Open Access Journals (Sweden)

    Apolinar Maya-Mendoza

    2010-04-01

    Full Text Available DNA synthesis must be performed with extreme precision to maintain genomic integrity. In mammalian cells, different genomic regions are replicated at defined times, perhaps to preserve epigenetic information and cell differentiation status. However, the molecular principles that define this S phase program are unknown. By analyzing replication foci within discrete chromosome territories during interphase, we show that foci which are active during consecutive intervals of S phase are maintained as spatially adjacent neighbors throughout the cell cycle. Using extended DNA fibers, we demonstrate that this spatial continuity of replication foci correlates with the genetic continuity of adjacent replicon clusters along chromosomes. Finally, we used bioinformatic tools to compare the structure of DNA foci with DNA domains that are seen to replicate during discrete time intervals of S phase using genome-wide strategies. Data presented show that a major mechanism of S phase progression involves the sequential synthesis of regions of the genome because of their genetic continuity along the chromosomal fiber.

  6. Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation.

    Science.gov (United States)

    Gupta, Ashish; Mehra, Parul; Dhar, Suman Kumar

    2008-08-01

    The mechanism of DNA replication initiation and progression is poorly understood in the parasites, including human malaria parasite Plasmodium falciparum. Using bioinformatics tools and yeast complementation assay, we identified a putative homologue of Saccharomyces cerevisiaeorigin recognition complex subunit 5 in P. falciparum (PfORC5). PfORC5 forms distinct nuclear foci colocalized with the replication foci marker proliferating cell nuclear antigen (PfPCNA) and co-immunoprecipitates with PCNA during early-to-mid trophozoite stage replicating parasites. Interestingly, these proteins separate from each other at the non-replicating late schizont stage, citing the evidence of the presence of both PCNA and ORC components in replication foci during eukaryotic DNA replication. PfORC1, another ORC subunit, colocalizes with PfPCNA and PfORC5 at the beginning of DNA replication, but gets degraded at the late schizont stage, ensuring the regulation of DNA replication in the parasites. Further, we have identified putative PCNA-interacting protein box in PfORC1 that may explain in part the colocalization of PfORC and PfPCNA. Additionally, use of specific DNA replication inhibitor hydroxyurea affects ORC5/PCNA foci formation and parasitic growth. These results strongly favour replication factory model in the parasites and confer great potential to understand the co-ordination between ORC and PCNA during eukaryotic DNA replication in general.

  7. Spherical aberration from trajectories in real and hard-edge ...

    Indian Academy of Sciences (India)

    (3)–(4) by comparing with spherical aberration obtained from the ensemble of particle trajectories. The scaled field gives the same focal length. 3. Particle trajectory. 3.1 Ray equation with aberration. The particle trajectory in a solenoid magnet with aberrations is governed by the third-order paraxial ray equation given in eq.

  8. Generalized beam quality factor of aberrated truncated Gaussian laser beams

    CSIR Research Space (South Africa)

    Mafusire, C

    2011-07-01

    Full Text Available The authors outline a theory for the calculation of the beam quality factor of an aberrated laser beam. They provide closed form equations that show that the beam quality factor of an aberrated Gaussian beam depends on all primary aberrations except...

  9. Growth Performance, Plasma Fatty Acids, Villous Height and Crypt Depth of Preweaning Piglets Fed with Medium Chain Triacylglycerol

    Directory of Open Access Journals (Sweden)

    Loh Teck Chwen

    2013-05-01

    Full Text Available A study was conducted to investigate the effects of feeding medium chain triacylglycerol (MCT on growth performance, plasma fatty acids, villus height and crypt depth in preweaning piglets. A total of 150 new born piglets were randomly assigned into one of three treatments: i Control (no MCT; ii MCT with milk (MCT+milk; iii MCT without milk (MCT+fasting. Body weight, plasma fatty acid profiles, villus height and crypt depth were measured. Final BW for the Control and MCT+fasting was lower (p<0.05 than MCT+milk. The piglets fed with MCT regardless of milk provision or fasting had greater medium chain fatty acids (MCFA than the Control. In contrast, the Control had greater long chain fatty acid (LCFA and unsaturated fatty acid (USFA than the MCT piglets. The piglets fed with MCT regardless of milk provision or fasting had higher villus height for the duodenum and jejunum after 6 h of feeding. Similar observations were found in piglets fed with MCT after 6 and 8 days of treatment. This study showed that feeding MCT to the piglets before weaning improved growth performance, with a greater concentration of MCT in blood plasma as energy source and a greater height of villus in duodenum, jejunum and ileum.

  10. A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation.

    Science.gov (United States)

    Paulus, U; Potten, C S; Loeffler, M

    1992-11-01

    The control mechanisms involved in regeneration of murine intestinal crypts after perturbations are presently not well understood. The existence of some feedback signals from the cells on the villus to the cells in the crypt has been suggested. However, some recent experimental data point to the fact that regeneration in the crypt starts very early after perturbation, at a time when the villus cell population has hardly changed. In particular, this early cell proliferative activity is seen specifically at the bottom of the crypt, i.e. in the presumed stem cell zone and furthest from the villus. The objective of this study was to investigate whether a new concept of regulation operating solely at the stem cell level could explain the present mass of accumulated data on the post-irradiation recovery, which is an extensively studied perturbation from the experimental point of view. In order to check its validity, the new concept was formalized as a mathematical simulation model thus enabling comparison with experimental data. The model describes the cellular development from stem cells to the mature villus cells. As a basic feature it is assumed that the self-maintenance and the cell cycle activity of the stem cells are controlled by the number of these cells in an autoregulatory fashion. The essential features of the experimental data (i.e. the recovery with time and the consistency between different types of measurements) can be very well reproduced by simulations using a range of model parameters. Thus, we conclude that stem cell autoregulation is a valid concept which could replace the villus crypt feedback concept in explaining the early changes after irradiation when the damage primarily affects the crypt. The question of the detailed nature of the control process requires further investigation.

  11. Direct Measurements of Human Colon Crypt Stem Cell Niche Genetic Fidelity: The Role of Chance in Non-Darwinian Mutation Selection

    Directory of Open Access Journals (Sweden)

    Haeyoun eKang

    2013-10-01

    Full Text Available Perfect human stem cell genetic fidelity would prevent aging and cancer. However, perfection would be difficult to achieve, and aging is universal and cancers common. A hypothesis is that because mutations are inevitable over a human lifetime, downstream mechanisms have evolved to manage the deleterious effects of beneficial and lethal mutations. In the colon, a crypt stem cell architecture reduces the number of mitotic cells at risk for mutation accumulation, and multiple niche stem cells ensure that a lethal mutation within any single stem cell does not lead to crypt death. In addition, the architecture of the colon crypt stem cell niche may harness probability or chance to randomly discard many beneficial mutations that might lead to cancer. An analysis of somatic chromosome copy number alterations (CNAs reveals a lack of perfect fidelity in individual normal human crypts, with age-related increases and higher frequencies in ulcerative colitis, a proliferative, inflammatory disease. The age-related increase in somatic CNAs appears consistent with relatively normal replication error and cell division rates. Surprisingly, and similar to point mutations in cancer genomes, the types of crypt mutations were more consistent with random fixation rather than selection. In theory, a simple non-Darwinian way to nullify selection is to reduce the size of the reproducing population. Fates are more determined by chance rather than selection in very small populations, and therefore selection may be minimized within small crypt niches. The desired effect is that many beneficial mutations that might lead to cancer are randomly lost by drift rather than fixed by selection. The subdivision of the colon into multiple very small stem cell niches may trade Darwinian evolution for non-Darwinian somatic cell evolution, capitulating to aging but reducing cancer risks.

  12. Direct measurements of human colon crypt stem cell niche genetic fidelity: the role of chance in non-darwinian mutation selection.

    Science.gov (United States)

    Kang, Haeyoun; Shibata, Darryl

    2013-10-14

    Perfect human stem cell genetic fidelity would prevent aging and cancer. However, perfection would be difficult to achieve, and aging is universal and cancers common. A hypothesis is that because mutations are inevitable over a human lifetime, downstream mechanisms have evolved to manage the deleterious effects of beneficial and lethal mutations. In the colon, a crypt stem cell architecture reduces the number of mitotic cells at risk for mutation accumulation, and multiple niche stem cells ensure that a lethal mutation within any single stem cell does not lead to crypt death. In addition, the architecture of the colon crypt stem cell niche may harness probability or chance to randomly discard many beneficial mutations that might lead to cancer. An analysis of somatic chromosome copy number alterations (CNAs) reveals a lack of perfect fidelity in individual normal human crypts, with age-related increases and higher frequencies in ulcerative colitis, a proliferative, inflammatory disease. The age-related increase in somatic CNAs appears consistent with relatively normal replication error and cell division rates. Surprisingly, and similar to point mutations in cancer genomes, the types of crypt mutations were more consistent with random fixation rather than selection. In theory, a simple "non-Darwinian" way to nullify selection is to reduce the size of the reproducing population. Fates are more determined by chance rather than selection in very small populations, and therefore selection may be minimized within small crypt niches. The desired effect is that many beneficial mutations that might lead to cancer are randomly lost by drift rather than fixed by selection. The subdivision of the colon into multiple very small stem cell niches may trade Darwinian evolution for non-Darwinian somatic cell evolution, capitulating to aging but reducing cancer risks.

  13. The correction of electron lens aberrations.

    Science.gov (United States)

    Hawkes, P W

    2015-09-01

    The progress of electron lens aberration correction from about 1990 onwards is chronicled. Reasonably complete lists of publications on this and related topics are appended. A present for Max Haider and Ondrej Krivanek in the year of their 65th birthdays. By a happy coincidence, this review was completed in the year that both Max Haider and Ondrej Krivanek reached the age of 65. It is a pleasure to dedicate it to the two leading actors in the saga of aberration corrector design and construction. They would both wish to associate their colleagues with such a tribute but it is the names of Haider and Krivanek (not forgetting Joachim Zach) that will remain in the annals of electron optics, next to that of Harald Rose. I am proud to know that both regard me as a friend as well as a colleague. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The aberrant retroesophageal right subclavian artery.

    Science.gov (United States)

    Seres-Sturm, M; Maros, T N; Seres-Sturm, L

    1985-01-01

    Two cases with arteria lusoria were found at 278 routine dissections. These arteria arise as the last branches of the aortic arch and have a retroesophageal position. At the crossing point, the esophagus narrows due to the groove caused by the artery. The appearance of this malposition is the consequence of the perturbation in the organo-genesis of the right dorsal aorta and fourth branchial artery. The aberration can lead to disphagia lusoria.

  15. Retrotracheal aberrant left brachiocephalic vein: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Yigit, Adalet E.; Haliloglu, Mithat; Karcaaltincaba, Musturay; Ariyurek, Macit O. [Hacettepe University Faculty of Medicine, Department of Radiology, Ankara (Turkey)

    2008-03-15

    We present a child with double aberrant left brachiocephalic vein (ALBCV) that was an incidental finding on CT. The anterior and thin branch was above the aortic arch and behind the truncus brachiocephalicus and drained into the superior vena cava (SVC). The posterior and thick branch of the ALBCV coursed posterior to the trachea and oesophagus and joined with the azygos vein before draining into the SVC. To our knowledge, retrotracheal ALBCV has not been previously described. (orig.)

  16. Aberrant attachment of orbicularis oculi: Case report

    Directory of Open Access Journals (Sweden)

    Sehgal Ritu

    2005-01-01

    Full Text Available A morphological peculiarity was observed in the form of an aberrant lateral bony attachment of the orbital part of the Orbicularis oculi muscle on the zygomatic bone, during routine dissection of a cadaver of an adult male of Indian origin. Fibers of this part of the muscle are not known to show any lateral attachment on bone. This paper discusses the presentation, probable embryological cause and clinical implications of this unusual finding.

  17. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  18. Regional cerebral blood flow in epileptic foci using (I-123) IMP-SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, Tohru (Toyama Medical and Pharmaceutical Univ. (Japan). Faculty of Medicine)

    1989-09-01

    Fifty-six epileptic patients, whose ages ranged from 6 months to 16 years (a mean age, 8 years and 2 months), were examined by single photon emission computed tomography (SPECT) with (I-123) N-isopropyl p-iodoamphetamine (IMP). Of these patients, 44 had partial seizures (PS) and 12 had generalized seizures (GS). SPECT revealed abnormality of regional cerebral blood flow (rCBF) in 24 PS patients (54.5%), being correlated with EEG abnormality. Among the 24 patients, 22 had a decreased rCBF and 2 others had an increased rCBF. According to the PS type, rCBF abnormality in the foci was less frequently observed for benign age-related partial epilepsy (2/9) than for the other types of partial epilepsy (22/35). Among 35 patients with the other types of partial epilepsy, SPECT showed foci in the frontal (12), central (3), parietal (4), temporal (6), and occipital (6) regions, and diffuse spike-wave or the lack of paroaxysmals (4). The EEG foci was of the left hemisphere in 12 patients, and of the right hemisphere in 18 patients. Higher incidence of rCBF abnormality was associated with the temporal, partietal, and frontal foci than with the occipital foci. There was no correlation between the incidence of rCBF abnormlaity and the frequency of seizure activities on EEG. Complex partial seizures had a tendency to be associated with rCBF abnormality. In comparing IMP uptake in evaluable 17 patients with a decreased rCBF, a mean %CBF in foci compared to that in the contralateral area was 91.9%. All of the 12 GS patients showed no focal reduction of rCBF around the cortex. Patients with tonic-clonic seizure and myoclonic seizure had almost normal IMP images. The IMP images of organic lesions were a marked reduction of rCBF. IMP-SPECT may also be suitable for evaluating the underlying organic and secondary involving disorders with epilepsy. (N.K.).

  19. An APC:WNT counter-current-like mechanism regulates cell division along the colonic crypt axis: a mechanism that explains how APC mutations induce proliferative abnormalities that drive colon cancer development.

    Directory of Open Access Journals (Sweden)

    Bruce M Boman

    2013-11-01

    Full Text Available APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside. WNT signaling, in contrast, is high at the bottom (where SCs reside and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g. survivin are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric. APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly-proliferating cells during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes.

  20. Effect of splenectomy on the size of amoebic liver abscesses and metastatic foci in hamsters.

    Science.gov (United States)

    Ghadirian, E; Meerovitch, E

    1981-01-01

    The role of the spleen in hepatic amoebiasis in hamsters was studied. In hamsters receiving an intrahepatic inoculation of 10(5) trophozoites of axenic Entamoeba histolytica at 7 or 14 days postsplenectomy, the mean weight of metastatic foci increased significantly when compared with sham-splenectomized or intact controls. In contrast, when both splenectomy and intrahepatic inoculation with amoebae were carried out at the same time, there was not only a significant increase in the mean weight of metastatic foci but also in the liver abscess. It is suggested that the spleen is important for host defense against E. histolytica infection, especially in the reduction in the degree of metastatic spread from the primary site. PMID:6260670

  1. Genomic aberrations in borderline ovarian tumors

    Directory of Open Access Journals (Sweden)

    Davidson Ben

    2010-02-01

    Full Text Available Abstract Background According to the scientific literature, less than 30 borderline ovarian tumors have been karyotyped and less than 100 analyzed for genomic imbalances by CGH. Methods We report a series of borderline ovarian tumors (n = 23 analyzed by G-banding and karyotyping as well as high resolution CGH; in addition, the tumors were analyzed for microsatellite stability status and by FISH for possible 6q deletion. Results All informative tumors were microsatellite stable and none had a deletion in 6q27. All cases with an abnormal karyotype had simple chromosomal aberrations with +7 and +12 as the most common. In three tumors with single structural rearrangements, a common breakpoint in 3q13 was detected. The major copy number changes detected in the borderline tumors were gains from chromosome arms 2q, 6q, 8q, 9p, and 13q and losses from 1p, 12q, 14q, 15q, 16p, 17p, 17q, 19p, 19q, and 22q. The series included five pairs of bilateral tumors and, in two of these pairs, informative data were obtained as to their clonal relationship. In both pairs, similarities were found between the tumors from the right and left side, strongly indicating that bilaterality had occurred via a metastatic process. The bilateral tumors as a group showed more aberrations than did the unilateral ones, consistent with the view that bilaterality is a sign of more advanced disease. Conclusion Because some of the imbalances found in borderline ovarian tumors seem to be similar to imbalances already known from the more extensively studied overt ovarian carcinomas, we speculate that the subset of borderline tumors with detectable imbalances or karyotypic aberrations may contain a smaller subset of tumors with a tendency to develop a more malignant phenotype. The group of borderline tumors with no imbalances would, in this line of thinking, have less or no propensity for clonal evolution and development to full-blown carcinomas.

  2. Wavefront aberrations of x-ray dynamical diffraction beams.

    Science.gov (United States)

    Liao, Keliang; Hong, Youli; Sheng, Weifan

    2014-10-01

    The effects of dynamical diffraction in x-ray diffractive optics with large numerical aperture render the wavefront aberrations difficult to describe using the aberration polynomials, yet knowledge of them plays an important role in a vast variety of scientific problems ranging from optical testing to adaptive optics. Although the diffraction theory of optical aberrations was established decades ago, its application in the area of x-ray dynamical diffraction theory (DDT) is still lacking. Here, we conduct a theoretical study on the aberration properties of x-ray dynamical diffraction beams. By treating the modulus of the complex envelope as the amplitude weight function in the orthogonalization procedure, we generalize the nonrecursive matrix method for the determination of orthonormal aberration polynomials, wherein Zernike DDT and Legendre DDT polynomials are proposed. As an example, we investigate the aberration evolution inside a tilted multilayer Laue lens. The corresponding Legendre DDT polynomials are obtained numerically, which represent balanced aberrations yielding minimum variance of the classical aberrations of an anamorphic optical system. The balancing of classical aberrations and their standard deviations are discussed. We also present the Strehl ratio of the primary and secondary balanced aberrations.

  3. Lawsonia intracellularis exploits β-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation.

    Directory of Open Access Journals (Sweden)

    Yang W Huan

    Full Text Available Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF and quantitative reverse transcriptase PCR (RTqPCR to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc. We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due

  4. Lawsonia intracellularis exploits β-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation.

    Science.gov (United States)

    Huan, Yang W; Bengtsson, Rebecca J; MacIntyre, Neil; Guthrie, Jack; Finlayson, Heather; Smith, Sionagh H; Archibald, Alan L; Ait-Ali, Tahar

    2017-01-01

    Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion

  5. Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells

    DEFF Research Database (Denmark)

    von der Maase, H

    1984-01-01

    The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost...... constant enhancement of the radiation response, the dose effect factor (DEF) being 1.19. The effect of BLM was extremely dependent on the sequence and interval between drug administration and irradiation. The most pronounced effect was observed when BLM was given 2 h before irradiation (DEF = 2.......40), at which interval the D0 surprisingly increased by a factor of 1.4. Administration of MM-C from 24 h before to 24 h after irradiation enhanced the radiation response. The effect peaked on administration 6 h before irradiation (DEF = 1.21) and diminished by application after irradiation. Cis-DDP enhanced...

  6. Imaging methods for detection of infectious foci. Les methodes scintigraphiques de detection des foyers infectieux

    Energy Technology Data Exchange (ETDEWEB)

    Couret, I.; Rossi, M. (Centre Hospitalier Universitaire, 34 - Montpellier (France)); Weinemann, P.; Moretti, J.L. (Hopital Avicenne, 93 - Bobigny (France) Paris-13 Univ., 93 - Saint-Denis (France))

    1993-01-01

    Several tracers can be used for imaging infection. None is a worthwhile agent for all infectious foci, but each one has preferential applications, depending on its uptake mechanism by the infectious and/or inflammatory focus. Autologous leucocytes labeled in vitro with indium-111 (In-111) or with technetium-99-hexamethylpropyleneamine oxime (Tc-99m HMPAO) were applied with success in the detection of peripheral bone infection, focal vascular graft infection and inflammatory bowel disease. Labeling with In-111 is of interest in chronic bone infection, while labeling with Tc-99m HMPAO gets the advantage of a better dosimetry and imaging. The interest of in vivo labeled leucocytes with a Tc-99m labeled monoclonal antigranulocyte antibody anti-NCA 95 (BW 250/183) was proved in the same principal type of infectious foci than in vitro labeled leucocytes. Sites of chronic infection in the spine and the pelvis, whether active or healed, appear as photopenic defects on both in vitro labeled leucocytes and Tc-99m monoclonal antigranulocyte antibody (BW 250/183) scintigraphies. With gallium-67 results showed a high sensitivity with a low specificity. This tracer demonstrated good performance to delineate foci of infectious spondylitis. In-111 and Tc-99m labeled polyclonal human immunoglobulin (HIG) was applied with success in the assessment of various infectious foci, particularly in chronic sepsis. As labeled leucocytes, labeled HIG showed cold defects in infectious sepsis of the spine. Research in nuclear medicine is very active in the development of more specific tracers of infection, mainly involved in Tc-99m or In-111 labeled chemotactic peptides, antigranulocyte antibody fragments, antibiotic derivatives and interleukins. (authors). 70 refs.

  7. Prevalence of Carcinomatous Foci in Oral Leukoplakia: A Clinicopathologic Study of 546 Indian Samples.

    Science.gov (United States)

    Gopinath, Divya; Thannikunnath, Beena Valappil; Neermunda, Salmanul Faris

    2016-08-01

    Oral Leukoplakia (OL), the most common potentially malignant disorder, is diagnosed clinically on the basis of exclusion of other lesions. In a country like India, where prevalence of oral cancer is very high, the issue of carcinomatous foci within OL at the time of initial diagnosis of leukoplakia has never been addressed before. To estimate the prevalence and risk factors for epithelial dysplasia as well as carcinoma within OL lesions at the time of initial clinical presentation in an Indian population with high prevalence of tobacco use. Clinical and pathologic data (age, sex, lesion location and histopathologic grading) of 546 cases of leukoplakia were analyzed. The prevalence rate of dysplasia and carcinoma in 546 oral leukoplakia cases was calculated. Univariate analysis was performed to examine risk factors associated with the presence of carcinoma and dysplasia within the lesions. The male to female ratio in this study was 2:1. Majority of the patients irrespective of sex had a history of tobacco use. Of the total 85% of non-homogeneous lesions and 70% for the homogeneous lesions were illustrating, features of epithelial dysplasia. The prevalence rate of carcinoma was 11.9%. In univariate analysis it was found that lesion site, clinical appearance, tobacco use were strongly correlated with the presence of carcinoma within OL. Our results demonstrate that majority of leukoplakia irrespective of its clinical appearance contain a dysplastic component and significant proportion contains carcinomatous foci. Lesions with certain features are more prone to have carcinomatous foci. However there is always a chance of finding foci of carcinoma in OL anywhere in the oral cavity. Therefore, excision biopsy is always mandatory before long term follow-up and treatment is planned.

  8. CDC25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci.

    Directory of Open Access Journals (Sweden)

    Rose Boutros

    Full Text Available CDK-cyclin complexes regulate centriole duplication and microtubule nucleation at specific cell cycle stages, although their exact roles in these processes remain unclear. As the activities of CDK-cyclins are themselves positively regulated by CDC25 phosphatases, we investigated the role of centrosomal CDC25B during interphase. We report that overexpression of CDC25B, as is commonly found in human cancer, results in a significant increase in centrin 2 at the centrosomes of interphase cells. Conversely, CDC25B depletion causes a loss of centrin 2 from the centrosome, which can be rescued by treatment with the proteasome inhibitor MG132. CDC25B overexpression also promotes the formation of excess centrin 2 "foci". These foci can accumulate other centrosome proteins, including γ-tubulin and PCM-1, and can function as microtubule organising centres, indicating that these represent functional centrosomes. Formation of centrin 2 foci can be blocked by specific inhibition of CDK2 but not CDK1. CDK2-mediated phosphorylation of Monopolar spindle 1 (Mps1 at the G1/S transition is essential for the initiation of centrosome duplication, and Mps1 is reported to phosphorylate centrin 2. Overexpression of wild-type or non-degradable Mps1 exacerbated the formation of excess centrin 2 foci induced by CDC25B overexpression, while kinase-dead Mps1 has a protective effect. Together, our data suggest that CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. Overexpression of CDC25B may therefore contribute to tumourigenesis by perturbing the natural turnover of centrosome proteins such as Mps1 and centrin 2, thus resulting in the de novo assembly of extra-numerary centrosomes and potentiating chromosome instability.

  9. Sanation of carious and periapical foci in young athletes with impairment of cardiovascular adaptation

    Directory of Open Access Journals (Sweden)

    I. I. Belyaev

    2014-01-01

    Full Text Available The aim of this study was to evaluate the impact of sanation of oral cavity in young athletes on the course of adaptation of the cardiovascular system to the condition of sports activities. According to the research results, it was revealed that the optimal period for sanation of periapical odontogenic foci in athletes with clinical signs of impairment (dysfunction of cardiovascular system adaptation to exercise stress was a preparatory training period, while carious lesion sanation required preparatory or postcompetition periods.

  10. Ocular aberrations in barn owl eyes.

    Science.gov (United States)

    Harmening, Wolf M; Vobig, Michael A; Walter, Peter; Wagner, Hermann

    2007-10-01

    Optical quality in barn owl eyes is presented in terms of measuring the ocular wavefront aberrations with a standard Tscherning-type wavefront aberrometer under natural viewing conditions. While accommodative state was uncontrolled, all eyes were focused within 0.4D with respect to the plane of the aberrometer. Total RMS wavefront error was between 0.06 and 0.15 microm (mean: 0.10 microm, STD: 0.03 microm, defocus cancelled) for a 6 mm pupil. The results suggest that image quality in barn owl eyes is excellent.

  11. Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype.

    Directory of Open Access Journals (Sweden)

    Stephanie Plog

    Full Text Available The human CLCA4 (chloride channel regulator, calcium-activated modulates the intestinal phenotype of cystic fibrosis (CF patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype.

  12. Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell HomeostasisSummary

    Directory of Open Access Journals (Sweden)

    Nicholas R. Smith

    2017-05-01

    Full Text Available Background & Aims: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs, it remains unclear what role cell adhesion plays in shaping the regulatory niche. Previously we have shown that the cell adhesion molecule and cancer stem cell marker, CD166/ALCAM (activated leukocyte cell adhesion molecule, is highly expressed by both active-cycling Lgr5+ ISCs and adjacent Paneth cells within the crypt base, supporting the hypothesis that CD166 functions to mediate ISC maintenance and signal coordination. Methods: Here we tested this hypothesis by analyzing a CD166–/– mouse combined with immunohistochemical, flow cytometry, gene expression, and enteroid culture. Results: We found that animals lacking CD166 expression harbored fewer active-cycling Lgr5+ ISCs. Homeostasis was maintained by expansion of the transit-amplifying compartment and not by slow-cycling Bmi1+ ISC stimulation. Loss of active-cycling ISCs was coupled with deregulated Paneth cell homeostasis, manifested as increased numbers of immature Paneth progenitors due to decreased terminal differentiation, linked to defective Wnt signaling. CD166–/– Paneth cells expressed reduced Wnt3 ligand expression and depleted nuclear β-catenin. Conclusions: These data support a function for CD166 as an important cell adhesion molecule that shapes the signaling microenvironment by mediating ISC–niche cell interactions. Furthermore, loss of CD166 expression results in decreased ISC and Paneth cell homeostasis and an altered Wnt microenvironment. Keywords: Intestinal Stem Cell, Homeostasis

  13. Rapid identification of paragonimiasis foci by lay informants in Lao People's Democratic Republic.

    Directory of Open Access Journals (Sweden)

    Peter Odermatt

    Full Text Available BACKGROUND: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases. METHODOLOGY/PRINCIPAL FINDINGS: The study was carried out in an endemic area of Lao People's Democratic Republic. Leaders of 49 remote villages in northern Vientiane Province were asked to notify suspected paragonimiasis patients using a four-item questionnaire sent through administrative channels: persons responding positively for having chronic cough (more than 3 weeks and/or blood in sputum with or without fever. We validated the village leaders' reports in ten representative villages with a door-to-door survey. We examined three sputa of suspected patients for the presence of Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and notified a total of 220 suspected patients; 76.2% were eventually confirmed; an additional 138 suspected cases were found in the survey. Sensitivity of village leaders' notice for "chronic cough" and "blood in sputum" was 100%; "blood in sputum" alone reached a sensitivity of 85.7%. SIGNIFICANCE: Our approach led to the identification of three previously unknown foci of transmission. A rapid and simple lay-informant questionnaire approach is a promising low-cost community diagnostic tool of paragonimiasis control programs.

  14. PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rudolph, Jeanette Heede [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Jakob, Burkhard [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Fink, Daniela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Tobias, Frank [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Blattner, Christine [Karlsruhe Inst. of Technology (KIT) (Germany). Inst. of Toxicology and Genetics; Taucher-Scholz, Gisela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany)

    2012-03-26

    The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. In this paper, we show that exposure of normal human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation in response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. Finally, we propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair.

  15. Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle.

    Directory of Open Access Journals (Sweden)

    Wesley H Stepp

    2017-10-01

    Full Text Available We have shown previously that Sp100 (a component of the ND10 nuclear body represses transcription, replication and establishment of incoming human papillomavirus (HPV DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection.

  16. High-amplitude pace mapping increases safety of radiofrequency catheter ablation of parahisian ectopic foci.

    Science.gov (United States)

    Mamchur, Sergey E; Kurilin, Mikhail Y

    2012-12-01

    The objective of the study is to assess the efficacy of high-amplitude pace mapping in terms of the atrioventricular (AV) block risk after radiofrequency catheter ablation (RCA) of parahisian ectopic foci. Twenty patients aged 38 ± 14 years with no structural heart disease underwent RCA of parahisian ectopic foci. All the patients were randomized into two groups: Group I (n = 11) had RCA performed in the region defined as ectopic focus by electrophysiology study and Group II (n = 9) had high-amplitude pacing performed in the region of "perfect" mapping. RCA was done only at the sites where high-amplitude pacing revealed the absence of His bundle capture. In group I, the efficacy of RCA was 54.5% and it was 100% in group II (P = 0.0195). Group II had no complications; in group I there were 27% of AV blocks (P = 0.0893). The late recurrence of ectopic activity was comparable in both groups: 3 (27%) and 2 (22%), respectively (P = 0.7953). In all the cases of recurrent ectopic activity and in all the cases of ineffective primary procedure, group I had effective reablation procedures performed using high-amplitude pace mapping. The overall efficacy in terms of repeated procedures was 90%. High-amplitude pace mapping increases primary and secondary efficacy of parahisian ectopic foci RCA and decreases the risk of AV block development. (PACE 2012;35:1458-1463). ©2012, The Authors. Research Institute for complex issues of Cardiovascular.

  17. The Underground Domed Crypt in the Mound no. 5 From the A.V. Tereshchenko’s Excavations in Tsarev Hillfort in 1843

    Directory of Open Access Journals (Sweden)

    Glukhov Aleksandr Anatolyevich

    2015-12-01

    Full Text Available The article is devoted to the A. Tereshchenko’s archaeological excavations of the underground domed crypt in 1843 in Tsarev hillfort - the second largest monument of the Golden Horde period in the Lower Volga located on the left bank of Akhtuba-river. Based on archival information, the author analyzes the circumstances of the underground crypt’s discovery, gives a description of the object. The author found that the crypt in Tsarev belongs to the type of cruciform crypts, located under the above-ground constructions (mausoleums. The constructions of this type have analogies on the territory of the Golden Horde, and in other regions: Central Asia, Azerbaijan, Turkmenistan. For the first time introduced into scientific circulation unique pattern of Golden Horde’s object was investigated by Tereschenko on Tsarev hillfort. This image is the only surviving graphics of excavated structures that Tereschenko was accompanied by his diaries and reports. The rest of the image are not kept or are not found in the archives yet. The article also gives a dating of the investigated construction. Copper coin of 766 AH (1364/64 A.D. found here to determine that burial structure was built no later than the mid-1360s. The author has taken into account the large size, complex structure, the findings made in the underground crypt and concluded that the burial complex, researched by Tereshchenko, was elitist. Use of comprehensive information (Tereshchenko’s diary descriptions, topographical plans of 1842-1843 and satellite images helped the author to locate the place of excavation of the crypt on the ground.

  18. AFSC/RACE/EcoFOCI - Ichthyoplankton data collected in support of FOCI assessment surveys and ecosystem observations in the Bering, Beaufort, and Chukchi Seas and the Gulf of Alaska 1972 to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The dataset contains records of fish eggs and larvae collected during FOCI assessment surveys. Records include all data pertinent to identify where specimens were...

  19. Aberrant Myokine Signaling in Congenital Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Masayuki Nakamori

    2017-10-01

    Full Text Available Summary: Myotonic dystrophy types 1 (DM1 and 2 (DM2 are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM, a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6 myokine signaling pathway in CDM muscles. We also found a correlation between muscle immaturity and not only IL-6 expression but also expanded CTG repeat length and CpG methylation status upstream of the repeats. Aberrant CpG methylation was associated with transcriptional dysregulation at the repeat locus, increasing the toxic RNA burden that upregulates IL-6. Because the IL-6 pathway is involved in myocyte maturation and muscle atrophy, our results indicate that enhanced RNA toxicity contributes to severe CDM phenotypes through aberrant IL-6 signaling. : Congenital myotonic dystrophy (CDM manifests characteristic genetic (very large CTG repeat expansions, epigenetic (CpG hypermethylation upstream of the repeat, and phenotypic (muscle immaturity features not seen in adult DM. Nakamori et al. find phenotype-genotype and epigenotype correlation in CDM muscle and reveal involvement of the IL-6 myokine signaling pathway in the disease process. Keywords: CTCF, ER stress, IL-6, muscular dystrophy, NF-κB, trinucleotide, cytokine, splicing

  20. Effect of Quartic Phase Optical Aberration on Laser Beam Quality

    Science.gov (United States)

    Bencheikh, A.; Bouafia, M.; Boubetra, Dj.

    2009-09-01

    Laser beam quality is related to the aberration effect. Quartic phase aberration, more commonly known as spherical aberration, can result from aberrated optical components such as beam expanding telescopes, focusing or collimating lenses, or other conventional optical elements; from thermal focusing or thermal blooming in high power laser windows, lenses, amplifier rods, optical isolators, and other absorbing media. In general any kind of quartic aberration will lead to increased far field beam spread, degraded laser beam focusability and increased values of the beam quality. Currently, a well established quality parameter for laser beams is the M2 factor. This paper presents a new mathematical set for the spherical aberration coefficient C4 of Gaussian beams. The main idea comes from the estimation of the laser beam quality factor M2 given by Siegman. We show that this coefficient concerns only the case of geometrical optics.

  1. Primary aberration coefficients for axial gradient-index lenses

    Science.gov (United States)

    Bociort, Florian

    1999-08-01

    As for homogeneous lenses, for axial gradients the analysis of the Seidel and chromatic aberration coefficients can be very useful in lens design. However, at present few commercial optical design programs list the Seidel aberrations of GRIN lenses and none of them lists the chromatic aberrations. In order to facilitate the computer implementation of the chromatic aberrations of axial GRIN lenses a new mathematical derivation for the axial and lateral color coefficients is presented. Also, new qualitative insight into the properties of axial GRIN lenses is obtained by introducing the thin-lens approximation in the aberration expressions. Within the domain of validity of this approximation, the primary aberrations of an axial GRIN lens are equivalent to those of a pair of homogeneous aspherical lens in contact, having a common plane surface and having refractive indices and Abbe numbers equal to the corresponding axial GRIN values at the two end surfaces.

  2. Hydronephrosis by an Aberrant Renal Artery: A Case Report

    OpenAIRE

    Park, Byoung Seok; Jeong, Taek Kyun; Ma, Seong Kwon; Kim, Soo Wan; Kim, Nam Ho; Choi, Ki Chul; Jeong, Yong Yeon

    2003-01-01

    Ureteropelvic junction obstruction is usually intrinsic and is most common in children. Aberrant renal arteries are present in about 30% of individuals. Aberrant renal arteries to the inferior pole cross anteriorly to the ureter and may cause hydronephrosis. To the best of our knowledge, although there are some papers about aberrant renal arteries producing ureteropelvic junction obstruction, there is no report of a case which is diagnosed by the new modalities, such as computed tomography an...

  3. Higher order aberrations of the eye: Part one

    Directory of Open Access Journals (Sweden)

    Marsha Oberholzer

    2016-03-01

    Full Text Available This article is the first in a series of two articles that provide a comprehensive literature review of higher order aberrations (HOAs of the eye. The present article mainly explains the general principles of such HOAs as well as HOAs of importance, and the measuring apparatus used to measure HOAs of the eye. The second article in the series discusses factors contributing to variable results in measurements of HOAs of the eye.Keywords: Higher order aberrations; wavefront aberrations; aberrometer

  4. AFSC/RACE/EcoFOCI: 2010 BEST and BSIERP Study 1WE10/WE10-08

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecosystem & Fisheries-Oceanography Coordinated Investigations (Eco-FOCI) is an effort by National Oceanic and Atmospheric Administration (NOAA) and associated...

  5. Human axial chromatic aberration found not to decline with age.

    Science.gov (United States)

    Ware, C

    1982-01-01

    Millodot (1976) reported a dramatic decline in the amount of axial chromatic aberration of the human eye with age. The present study represents a failure to replicate that finding using a more standard procedure. No difference in chromatic aberration was found between a young and an older group of observers. Also, the chromatic aberrations of two observers which had been measured 25 years previously showed no decline when these measurements were repeated, even though their ages at first and second testing straddled the period over which Millodot reported the most change in chromatic aberration.

  6. Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

    Science.gov (United States)

    Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

    2014-01-01

    The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

  7. Effect of antioxidants on X-ray-induced γ-H2AX foci in human blood lymphocytes: preliminary observations.

    Science.gov (United States)

    Kuefner, Michael A; Brand, Michael; Ehrlich, James; Braga, Larissa; Uder, Michael; Semelka, Richard C

    2012-07-01

    To investigate the effect of a radioprotective oral agent containing a formulation of antioxidants and glutathione-elevating compounds on the extent of x-ray-induced γ-H2AX foci formation. The study was approved by local ethics committee and informed consent was obtained from each subject. In vitro experiments with blood lymphocytes of 25 healthy volunteers were performed without antioxidants and with antioxidants added either before or immediately after irradiation (10 mGy). For in vivo/in vitro tests, blood samples were obtained before, 15, 30, and 60 minutes (n=17) after, and 2, 3, and 5 hours (n=11) after oral ingestion of antioxidant pills and were irradiated (10 mGy). DNA double-strand breaks (DSBs) were quantified in isolated lymphocytes 5 minutes (in vitro and in vivo/in vitro) and 15 minutes (in vitro) after irradiation by enumerating γ-H2AX foci. To validate the data, additional in vitro experiments with use of 53BP1 as another independent marker for DSBs were performed. Nonirradiated samples served as controls. Statistical analyses were performed by using Wilcoxon rank-sum tests (in vitro), repeated-measures test, and Dunnett test (in vivo/in vitro). In the in vitro experiments, 15-minute preincubation with antioxidants significantly reduced mean γ-H2AX foci levels by 23% (Plead to a reduction of x-ray-induced foci (P=.6905). Mean 53BP1 foci were also reduced by preincubation with the radioprotectant. In the in vivo/in vitro tests, oral pretreatment with antioxidants also led to a significant reduction of γ-H2AX foci formation; administration 60 minutes before irradiation resulted in a mean foci reduction of 58% (Pleads to a significant reduction in foci. © RSNA, 2012.

  8. White matter abnormalities in the anterior temporal lobe suggest the side of the seizure foci in temporal lobe epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Y.; Yagishita, A. [Tokyo Metropolitan Neurological Hospital, Department of Neuroradiology, Fuchu, Tokyo (Japan); Arai, N. [Tokyo Metropolitan Neurological Institute, Department of Clinical Neuropathology, Fuchu, Tokyo (Japan)

    2006-07-15

    White matter abnormalities in the anterior temporal lobe (WAATL) are sometimes observed on magnetic resonance (MR) images of patients with temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in TLE patients. We reviewed 112 consecutive patients with medically intractable TLE. We compared the side of seizure foci on EEG (preoperative and intraoperative) and MR images. Both loss of gray-white matter demarcation and increased signal intensity changes in the anterior white matter (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were present on the same side as the seizure foci on preoperative intracranial EEG with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG) in all the patients. In 47 patients, MR images showed WAATL and focal lesions that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45 patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion were on the same side. In three patients, no focal lesions were seen but WAATL were present on the same side as the seizure foci on sEEG and ECG. In four patients, MR images showed focal lesions for which epileptogenicity was questionable, and WAATL on the same side as the seizure foci on EEG. WAATL are clinically useful because they indicate the side of the seizure foci. (orig.)

  9. Age-related disease association of endogenous γ-H2AX foci in mononuclear cells derived from leukapheresis.

    Directory of Open Access Journals (Sweden)

    Shepherd H Schurman

    Full Text Available The phosphorylated form of histone H2AX (γ-H2AX forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ~57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10 and in sleep apnea patients (44%, p<0.10. Among patients ≥57 y/o, we found a significant (p = 0.037 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases.

  10. Accumulation of spontaneous γH2AX foci in long-term cultured mesenchymal stromal cells.

    Science.gov (United States)

    Pustovalova, Margarita; Grekhova, Anna; Astrelina, Тatiana; Nikitina, Viktoria; Dobrovolskaya, Ekaterina; Suchkova, Yulia; Kobzeva, Irina; Usupzhanova, Darya; Vorobyeva, Natalia; Samoylov, Aleksandr; Bushmanov, Andrey; Ozerov, Ivan V; Zhavoronkov, Alex; Leonov, Sergey; Klokov, Dmitry; Osipov, Andreyan N

    2016-12-11

    Expansion of mesenchymal stromal/stem cells (MSCs) used in clinical practices may be associated with accumulation of genetic instability. Understanding temporal and mechanistic aspects of this process is important for improving stem cell therapy protocols. We used γH2AX foci as a marker of a genetic instability event and quantified it in MSCs that undergone various numbers of passage (3-22). We found that γH2AX foci numbers increased in cells of late passages, with a sharp increase at passage 16-18. By measuring in parallel foci of ATM phosphorylated at Ser-1981 and their co-localization with γaH2AX foci, along with differentiating cells into proliferating and resting by using a Ki67 marker, we conclude that the sharp increase in γH2AX foci numbers was ATM-independent and happened predominantly in proliferating cells. At the same time, gradual and moderate increase in γH2AX foci with passage number seen in both resting and proliferating cells may represent a slow, DNA double-strand break related component of the accumulation of genetic instability in MSCs. Our results provide important information on selecting appropriate passage numbers exceeding which would be associated with substantial risks to a patient-recipient, both with respect to therapeutic efficiency and side-effects related to potential neoplastic transformations due to genetic instability acquired by MSCs during expansion.

  11. Aberrant intestinal microbiota in individuals with prediabetes

    DEFF Research Database (Denmark)

    Allin, Kristine H; Tremaroli, Valentina; Caesar, Robert

    2018-01-01

    AIMS/HYPOTHESIS: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut...... among individuals with prediabetes (mean log2 fold change -1.74 (SEM 0.41), p adj  = 2 × 10-3 and -1.65 (SEM 0.34), p adj  = 4 × 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did...... with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation. RESULTS: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals...

  12. Overlapped Fourier coding for optical aberration removal

    Science.gov (United States)

    Horstmeyer, Roarke; Ou, Xiaoze; Chung, Jaebum; Zheng, Guoan; Yang, Changhuei

    2014-01-01

    We present an imaging procedure that simultaneously optimizes a camera’s resolution and retrieves a sample’s phase over a sequence of snapshots. The technique, termed overlapped Fourier coding (OFC), first digitally pans a small aperture across a camera’s pupil plane with a spatial light modulator. At each aperture location, a unique image is acquired. The OFC algorithm then fuses these low-resolution images into a full-resolution estimate of the complex optical field incident upon the detector. Simultaneously, the algorithm utilizes redundancies within the acquired dataset to computationally estimate and remove unknown optical aberrations and system misalignments via simulated annealing. The result is an imaging system that can computationally overcome its optical imperfections to offer enhanced resolution, at the expense of taking multiple snapshots over time. PMID:25321982

  13. Genomic aberrations in normal tissue adjacent to HER2-amplified breast cancers: field cancerization or contaminating tumor cells?

    Science.gov (United States)

    Sadanandam, Anguraj; Lal, Aseem; Benz, Stephen C; Eppenberger-Castori, Serenella; Scott, Gary; Gray, Joe W; Spellman, Paul; Waldman, Fred; Benz, Christopher C

    2012-12-01

    Field cancerization effects as well as isolated tumor cell foci extending well beyond the invasive tumor margin have been described previously to account for local recurrence rates following breast conserving surgery despite adequate surgical margins and breast radiotherapy. To look for evidence of possible tumor cell contamination or field cancerization by genetic effects, a pilot study (Study 1: 12 sample pairs) followed by a verification study (Study 2: 20 sample pairs) were performed on DNA extracted from HER2-positive breast tumors and matching normal adjacent mammary tissue samples excised 1-3 cm beyond the invasive tumor margin. High-resolution molecular inversion probe (MIP) arrays were used to compare genomic copy number variations, including increased HER2 gene copies, between the paired samples; as well, a detailed histologic and immunohistochemical (IHC) re-evaluation of all Study 2 samples was performed blinded to the genomic results to characterize the adjacent normal tissue composition bracketing the DNA-extracted samples. Overall, 14/32 (44 %) sample pairs from both studies produced genome-wide evidence of genetic aberrations including HER2 copy number gains within the adjacent normal tissue samples. The observed single-parental origin of monoallelic HER2 amplicon haplotypes shared by informative tumor-normal pairs, as well as commonly gained loci elsewhere on 17q, suggested the presence of contaminating tumor cells in the genomically aberrant normal samples. Histologic and IHC analyses identified occult 25-200 μm tumor cell clusters overexpressing HER2 scattered in more than half, but not all, of the genomically aberrant normal samples re-evaluated, but in none of the genomically normal samples. These genomic and microscopic findings support the conclusion that tumor cell contamination rather than genetic field cancerization represents the likeliest cause of local clinical recurrence rates following breast conserving surgery, and mandate caution

  14. Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells.

    Science.gov (United States)

    Franken, Nicolaas A P; Hovingh, Suzanne; Ten Cate, Rosemarie; Krawczyk, Przemek; Stap, Jan; Hoebe, Ron; Aten, Jacob; Barendsen, Gerrit W

    2012-03-01

    Ionizing radiation-induced foci (IRIF) of DNA repair-related proteins accumulated at DNA double-strand break (DSB) sites have been suggested to be a powerful biodosimetric tool. However, the relationship between IRIF induction and biologically relevant endpoints, such as cell death and formation of chromosome rearrangements is less clear, especially for high linear energy transfer (LET) radiation. It is thus not sufficiently established whether IRIF are valid indicators of biological effectiveness of the various radiation types. This question is more significant in light of the recent advancements in light ion-beam and radionuclide therapy. Dose-effect relationships were determined for the induction of DNA-DSBs, chromosome aberrations and reproductive cell death in cultured SW-1573 cells irradiated with γ-rays from a Cs-137 source or with α-particles from an Am-241 source. Values of relative biological effectiveness (RBE) of the high LET α-particles were derived for these effects. DNA-DSB were detected by scoring of γ-H2AX foci, chromosome aberrations by fragments and translocations using premature chromosome condensation and cell survival by colony formation. Analysis of dose-effect relations was based on the linear-quadratic model. Except for the survival curves, for other effects no significant contribution was derived of the quadratic term in the range of doses up to 2 Gy of γ-rays. Calculated RBE values derived for the linear component of dose-effect relations for γ-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0±0.3, 14.7±5.1, 15.3±5.9 and 13.3±6.0, respectively. RBE values calculated at a certain biological effect level are 1, 4, 13 and 13, respectively. The RBE values derived from the LQ model are preferred as they are based on clinically relevant doses. The results show that with low LET radiation only a small fraction of the numerous DNA-DSBs yield chromosome damage and reproductive cell death. It is

  15. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    Full Text Available Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci.We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks.Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  16. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  17. Étude cytogenetique des aberrations chromosomiques chez des ...

    African Journals Online (AJOL)

    After 48 hours of culture in the presence of BrdU, the samples underwent the whole procedure of the metaphase cytogenetic analysis technique. Results: The 22 technicians totaled 4856 metaphases containing 421 chromosomal aberrations and 28 sister chromatid exchanges. It was noted the complex aberrations ...

  18. Numerical correction of aberrations via phase retrieval with speckle illumination

    DEFF Research Database (Denmark)

    Almoro, Percival; Gundu, Phanindra Narayan; Hanson, Steen Grüner

    2009-01-01

    What we believe to be a novel technique for wavefront aberration measurement using speckle patterns is presented. The aberration correction is done numerically. A tilted lens is illuminated with a partially developed speckle field, and the transmitted light intensity is sampled at axially displaced...

  19. An aberrant uterus: Case report | Ondieki | East African Medical ...

    African Journals Online (AJOL)

    A case of an aberrant uterus is presented and literature reviewed. The patient presented with abnormal uterine bleeding, left iliac fossa pain and was managed by excising the aberrant uterus. This case was an enigma as it didn't present in the classical way one with anomalies of the uterus would present. Despite ...

  20. Aberrant Breast in a Rare Site: A Case Report

    Directory of Open Access Journals (Sweden)

    Levent Yeniay

    2012-01-01

    Full Text Available Aberrant breast tissue is an anomaly in the embryogenesis of the breast that is found along the mammary ridge or out of that line. We report a case of a 71-year-old female patient with an abdominal aberrant breast tissue found incidentally in a piece of mesenteric biopsy. The histological features were consistent with breast tissue.

  1. Smad7 foci are present in micronuclei induced by heavy particle radiation.

    Science.gov (United States)

    Wang, Minli; Saha, Janapriya; Cucinotta, Francis A

    2013-08-30

    DNA damage and reactive oxygen species (ROS) generated by ionizing radiation (IR) activate DNA damage response (DDR) and cytokine signaling pathways, including double strand break (DSB) repair and TGFβ/Smad signaling pathway. Proteins assembled at IR-induced DSB sites can be visualized as foci, including γH2AX, 53BP1, ATM and ATF2. Unrepaired DSBs are thought to be one origin of micronuclei (MN), an indicator of genotoxic stress and chromosomal instability. Studies have detected γH2AX in IR-induced MN, indicating the presence of DSB in MN. Previously we reported that TGFβ downstream proteins Smad7 and phospho-Smad2 (pSmad2) co-localized with DDR proteins following radiation. Here we studied the status of Smad7 and pSmad2 in MN post high linear energy transfer (LET) radiation in human normal and cancerous cells. We observed γH2AX foci in IR-induced MN, whereas 53BP1 and ATF2 were absent. Interestingly, Smad7 foci, but not pSmad2, were detectable in both spontaneous and IR-induced MN. We compared the effect of particle track structures on the yield of MN using 5.6MeV/u boron (B) and 600MeV/u iron (Fe) particles with similar LET (200 and 180keV/μm, respectively) in human fibroblasts. The frequency of MN induced by B was lower than that by Fe particles, albeit the proportion of Smad7-positive to Smad7-negative MN remained constant. An increased frequency of spontaneous MN, with slightly higher ratio of Smad7 or γH2AX positive, was found in human prostate cancer cells (PC3) compared to normal cells. 24h after 1Gy of Fe particles exposure, the yield of MN increased, and the majority (∼70%) carried γH2AX and Smad7. Phospho-ATM (Ser1981) foci were found in both spontaneous and IR-induced MN in PC3 cells, displaying a much lower frequency compared to γH2AX and Smad7. Our data suggest a unique role of Smad7 in IR-induced MN formation, which may associate with DNA repair, apoptosis and genomic instability. Copyright © 2013. Published by Elsevier B.V.

  2. Why should I share my knowledge? A multiple foci of commitment perspective

    DEFF Research Database (Denmark)

    Swart, Juani; Kinnie, Nicholas; van Rossenberg, Yvonne Gerarda Theodora

    2014-01-01

    Knowledge-intensive firms need to leverage their individual knowledge assets via knowledge sharing to create collective knowledge resources. This process is, however, in the control of the knowledge worker. We explore this personal and emotive quality of knowledge sharing by asking: ‘How does...... employee commitment impact on knowledge sharing?’ We study professional service firms operating in cross-boundary environments and examine the impact of commitment to the organisation, profession, team and client on knowledge sharing. The article contributes directly to our understanding...... of the interrelationship between (a) the types and foci of commitment and (b) bidirectional knowledge sharing....

  3. Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

    Science.gov (United States)

    Barash, N. R.; Nosala, C.; Pham, J. K.; McInally, S. G.; Gourguechon, S.; McCarthy-Sinclair, B.

    2017-01-01

    ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand

  4. [Possible influences of climatic changes on the spread and intensity of foci of some human helminthiases].

    Science.gov (United States)

    Artamoshin, A S; Khodakova, V I

    2000-01-01

    Climatic changes on the Earth and in some of its regions have caused and will cause alterations in the natural and social factors which may influence the circulation of causative agents of helminthiases that develop both on land and in water with the participation of hydrobiont. These include changes in the size of the first and second intermediate hosts, in the hydrological conditions of water reservoirs, in the amount of precipitation, soil moisture, heat, etc. Therefore, the expected global warming may alter the areas of some helminths, the intensity of foci, etc.

  5. LKB1-AMPK modulates nutrient-induced changes in the mode of division of intestinal epithelial crypt cells in mice.

    Science.gov (United States)

    Blackmore, Katherine; Zhou, Weinan; Dailey, Megan J

    2017-09-01

    Nutrient availability influences intestinal epithelial stem cell proliferation and tissue growth. Increases in food result in a greater number of epithelial cells, villi height and crypt depth. We investigated whether this nutrient-driven expansion of the tissue is the result of a change in the mode of intestinal epithelial stem cell division and if LKB1-AMPK signaling plays a role. We utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice were separated into four groups and fed varying amounts of chow for 18 h: (1) ad libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h and refed. Mice were sacrificed, intestinal sections excised and immunohistochemically processed to determine the mitotic spindle orientation. Epithelial organoids in vitro were treated with no (0 mM), low (5 mM) or high (20 mM) amounts of glucose with or without an activator (Metformin) or inhibitor (Compound C) of LKB1-AMPK signaling. Cells were then processed to determine the mode of stem cell division. Fasted mice show a greater % of asymmetrically dividing cells compared with the other feeding groups. Organoids incubated with 0 mM glucose resulted in a greater % of asymmetrically dividing cells compared with the low or high-glucose conditions. In addition, LKB1-AMPK activation attenuated the % of symmetric division normally seen in high-glucose conditions. In contrast, LKB1-AMPK inhibition attenuated the % of asymmetric division normally seen in no glucose conditions. These data suggest that nutrient availability dictates the mode of division and that LKB1-AMPK mediates this nutrient-driven effect on intestinal epithelial stem cell proliferation. Impact statement The underlying cell biology of changes in the polarity of mitotic spindles and its relevance to tissue growth is a new concept and, thus, these data provide novel findings to begin to explain how this process contributes to the regeneration and growth of tissues. We

  6. Criteria for correction of quadratic field-dependent aberrations.

    Science.gov (United States)

    Zhao, Chunyu; Burge, James H

    2002-11-01

    Aberrations of imaging systems can be described by using a polynomial expansion of the dependence on field position, or the off-axis distance of a point object. On-axis, or zero-order, aberrations can be calculated directly. It is well-known that aberrations with linear field dependence can be calculated and controlled by using the Abbe sine condition, which evaluates only on-axis behavior. We present a new set of relationships that fully describe the aberrations that depend on the second power of the field. A simple set of equations is derived by using Hamilton's characteristic functions and simplified by evaluating astigmatism in the pupil. The equations, which we call the pupil astigmatism criteria, use on-axis behavior to evaluate and control all aberrations with quadratic dependence on the field and arbitrary dependence on the pupil. These relations are explained and are validated by using several specific optical designs.

  7. Prospects for electron beam aberration correction using sculpted phase masks

    Energy Technology Data Exchange (ETDEWEB)

    Shiloh, Roy, E-mail: royshilo@post.tau.ac.il; Remez, Roei; Arie, Ady

    2016-04-15

    Technological advances in fabrication methods allowed the microscopy community to take incremental steps towards perfecting the electron microscope, and magnetic lens design in particular. Still, state of the art aberration-corrected microscopes are yet 20–30 times shy of the theoretical electron diffraction limit. Moreover, these microscopes consume significant physical space and are very expensive. Here, we show how a thin, sculpted membrane is used as a phase-mask to induce specific aberrations into an electron beam probe in a standard high resolution TEM. In particular, we experimentally demonstrate beam splitting, two-fold astigmatism, three-fold astigmatism, and spherical aberration. - Highlights: • Thin membranes can be used as aberration correctors in electron columns. • We demonstrate tilt, twofold-, threefold-astigmatism, and spherical aberrations. • Experimental and physical-optics simulation results are in good agreement. • Advantages in cost, size, nonmagnetism, and nearly-arbitrary correction.

  8. Binocular visual performance and summation after correcting higher order aberrations.

    Science.gov (United States)

    Sabesan, Ramkumar; Zheleznyak, Len; Yoon, Geunyoung

    2012-12-01

    Although the ocular higher order aberrations degrade the retinal image substantially, most studies have investigated their effect on vision only under monocular conditions. Here, we have investigated the impact of binocular higher order aberration correction on visual performance and binocular summation by constructing a binocular adaptive optics (AO) vision simulator. Binocular monochromatic aberration correction using AO improved visual acuity and contrast sensitivity significantly. The improvement however, differed from that achieved under monocular viewing. At high spatial frequency (24 c/deg), the monocular benefit in contrast sensitivity was significantly larger than the benefit achieved binocularly. In addition, binocular summation for higher spatial frequencies was the largest in the presence of subject's native higher order aberrations and was reduced when these aberrations were corrected. This study thus demonstrates the vast potential of binocular AO vision testing in understanding the impact of ocular optics on habitual binocular vision.

  9. Hydronephrosis by an Aberrant Renal Artery: A Case Report

    Science.gov (United States)

    Park, Byoung Seok; Jeong, Taek Kyun; Ma, Seong Kwon; Kim, Soo Wan; Kim, Nam Ho; Choi, Ki Chul; Jeong, Yong Yeon

    2003-01-01

    Ureteropelvic junction obstruction is usually intrinsic and is most common in children. Aberrant renal arteries are present in about 30% of individuals. Aberrant renal arteries to the inferior pole cross anteriorly to the ureter and may cause hydronephrosis. To the best of our knowledge, although there are some papers about aberrant renal arteries producing ureteropelvic junction obstruction, there is no report of a case which is diagnosed by the new modalities, such as computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA). We describe a 36-year-old woman with right hydronephrosis. Kidney ultrasonogram and excretory urogram revealed right hydronephrosis. CTA and MRA clearly displayed an aberrant renal artery and hydronephrosis. The patient underwent surgical exploration. For the evaluation of hydronephrosis by an aberrant renal artery, use of CTA and MRA is advocated. PMID:12760271

  10. Aberration-corrected STEM: current performance and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Nellist, P D [Department of Physics, University of Dublin, Trinity College, Dublin 2 (Ireland); Chisholm, M F [Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6030 (United States); Lupini, A R [Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6030 (United States); Borisevich, A [Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6030 (United States); Jr, W H Sides [Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6030 (United States); Pennycook, S J [Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6030 (United States); Dellby, N [Nion Co., 1102 8th St., Kirkland, WA 98033 (United States); Keyse, R [Nion Co., 1102 8th St., Kirkland, WA 98033 (United States); Krivanek, O L [Nion Co., 1102 8th St., Kirkland, WA 98033 (United States); Murfitt, M F [Nion Co., 1102 8th St., Kirkland, WA 98033 (United States); Szilagyi, Z S [Nion Co., 1102 8th St., Kirkland, WA 98033 (United States)

    2006-02-22

    Through the correction of spherical aberration in the scanning transmission electron microscope (STEM), the resolving of a 78 pm atomic column spacing has been demonstrated along with information transfer to 61 pm. The achievement of this resolution required careful control of microscope instabilities, parasitic aberrations and the compensation of uncorrected, higher order aberrations. Many of these issues are improved in a next generation STEM fitted with a new design of aberration corrector, and an initial result demonstrating aberration correction to a convergence semi-angle of 40 mrad is shown. The improved spatial resolution and beam convergence allowed for by such correction has implications for the way in which experiments are performed and how STEM data should be interpreted.

  11. Image based method for aberration measurement of lithographic tools

    Science.gov (United States)

    Xu, Shuang; Tao, Bo; Guo, Yongxing; Li, Gongfa

    2018-01-01

    Information of lens aberration of lithographic tools is important as it directly affects the intensity distribution in the image plane. Zernike polynomials are commonly used for a mathematical description of lens aberrations. Due to the advantage of lower cost and easier implementation of tools, image based measurement techniques have been widely used. Lithographic tools are typically partially coherent systems that can be described by a bilinear model, which entails time consuming calculations and does not lend a simple and intuitive relationship between lens aberrations and the resulted images. Previous methods for retrieving lens aberrations in such partially coherent systems involve through-focus image measurements and time-consuming iterative algorithms. In this work, we propose a method for aberration measurement in lithographic tools, which only requires measuring two images of intensity distribution. Two linear formulations are derived in matrix forms that directly relate the measured images to the unknown Zernike coefficients. Consequently, an efficient non-iterative solution is obtained.

  12. p53 aberrations in low grade endometrioid carcinoma of the endometrium with nodal metastases: possible insights on pathogenesis discerned from immunohistochemistry.

    Science.gov (United States)

    Fadare, Oluwole; Parkash, Vinita

    2017-11-14

    TP53 mutations are rarely identified in low grade endometrioid carcinoma of the endometrium, and their pathogenic significance in such tumors is evidenced by the fact that TP53 aberrations have been associated with reduced recurrence-free survival in this subset of tumors. However, TP53 aberrations may not always represent a driving molecular event in a given endometrial cancer with a mutation. In this case study, the immunophenotype of a distinctive low grade endometrioid adenocarcinoma with an unusual pattern of lymph node metastases is used to explore the possible roles for underlying TP53-related molecular events in its pathogenesis. A low grade endometrioid carcinoma, 9 cm in greatest dimension, with 35% invasion of the myometrial wall thickness, focal lymphovascular invasion, and metastases to 2 of 16 pelvic lymph nodes, was diagnosed in a 52-year-old woman. The endometrial tumor showed a p53-mutation (aberrant)-type immunohistochemical pattern in 40% of the tumor, but the rest of the tumor, as well as the foci of myometrial and lymphovascular invasion, were p53-wild type. Both lymph nodes with metastatic disease showed a distinct biphasic pattern, comprised of both p53-wild type and p53-aberrant areas in tumoral foci that were spatially apposed but not intermixed. Most p53-aberrant areas (at both the lymph nodes and the endometrium) showed a higher mitotic index and increased atypia as compared to the p53-wild type areas; both showed squamous differentiation. The p53-aberrant areas at both locations were also p16-diffusely positive, vimentin-positive, and estrogen/progesterone receptor-positive, whereas the p53-wild type areas showed an identical immunophenotype with the exception of being p16-mosaic positive. All components of the tumor at both the primary and metastatic sites showed loss of MSH2 and MSH6 and retained MLH/PMS2 expression. The presence of p53-mutant and wild-type areas in multiple lymph nodes, coupled with the absence of a p53-aberrant

  13. Validation of JCountPro software for efficient assessment of ionizing radiation-induced foci in human lymphocytes.

    Science.gov (United States)

    Jakl, Lukáš; Lobachevsky, Pavel; Vokálová, Lenka; Durdík, Matúš; Marková, Eva; Belyaev, Igor

    2016-12-01

    Ionizing radiation-induced foci (IRIF) known also as DNA repair foci represent the most sensitive and specific assay for assessing DNA double-strand break (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to phosphorylated γH2AX and 53BP1. Although several approaches and software packages were developed for quantification of IRIF, not one of them was commonly accepted and inter-laboratory variability in the outputs was reported. In this study, JCountPro software was validated for IRIF enumeration in two independent laboratories. Human lymphocytes were γ-irradiated at doses of 0, 2, 5, 10 and 50 cGy. The cells were fixed, permeabilized and IRIF were immunostained using appropriate antibodies. Cell images were acquired with automatic Metafer system. Endogenous and radiation-induced γH2AX and 53BP1 foci were enumerated using JCountPro. This analysis was performed from the same cell galleries by the researchers from two laboratories. Yield of foci was analyzed by either arithmetic mean (AM) value (foci/cell) or principal average (PA) derived from the approximation of foci distribution with Poisson statistics. Statistical analysis was performed using factorial ANOVA. Enumeration of 53BP1, γH2AX and co-localized 53BP1/γH2AX foci by JCountPro was essentially the same between laboratories. IRIF were detected at all doses and linear dose response was obtained in the studied dose range. PA values from Poisson distribution fitted the data better as compared to AM values and were more powerful and sensitive for IRIF analysis than the AM values. All JCountPro data were confirmed by visual focus enumeration. We concluded that the JCountPro software was efficient in objectively enumerating IRIF regardless of an individual researcher's bias and has a potential for usage in clinics and molecular epidemiology.

  14. Origins of recently emerged foci of the tick Dermacentor reticulatus in central Europe inferred from molecular markers.

    Science.gov (United States)

    Kloch, Agnieszka; Mierzejewska, Ewa J; Karbowiak, Grzegorz; Slivinska, Kateryna; Alsarraf, Mohammed; Rodo, Anna; Kowalec, Maciej; Dwużnik, Dorota; Didyk, Yuliya M; Bajer, Anna

    2017-04-15

    The ornate dog tick Dermacentor reticulatus is vector of several blood parasites, including Babesia canis, a causative agent of babesiosis. The geographical range of D. reticulatus in Europe is discontinuous with a gap separating eastern and western macroregions. New foci observed in several locations in western and central Europe were considered an expansion of the western population, including foci in western Poland. In the present paper we used molecular markers to identify the origins of these foci, and we compared their genetic polymorphism to D. reticulatus collected in sites situated within the eastern population. The overall polymorphism in mt 16S rDNA was low, and all sites from the western population shared the same haplotype suggesting the expansion in this area. In the marker 5.8S rDNA-ITS2 we found no differences in polymorphism between sites from eastern Poland (eastern population), and newly emerged foci in western Poland considered a putative expansion zone of the western population. However, the sites from western Poland differed considerably from nearby German site. Our results show that foci in western Poland could not have originated from D. reticulatus from the western population, as previously thought. We found that the state border following river hinders considerably gene flow between adjacent sites what suggest that natural dispersal of D. reticulatus by wildlife is unlikely, and the emergence of new foci should rather be contributed to human-associated dispersal. We propose that livestock, and pets travelling with their owners are the most probable source of new foci, and they can easily transfer ticks within a country but not between countries. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Differential expression of proteins involved in energy production along the crypt-villus axis in early-weaning pig small intestine.

    Science.gov (United States)

    Xiong, Xia; Yang, Huansheng; Tan, Bie; Yang, Chengbo; Wu, Miaomiao; Liu, Gang; Kim, Sung Woo; Li, Tiejun; Li, Lili; Wang, Junjun; Wu, Guoyao; Yin, Yulong

    2015-08-15

    Weaning of piglets reflects intestinal dysfunction and atrophy and affected the physiological state of enterocytes. However, few studies have defined physiological state of enterocytes along the crypt-villus axis in early-weaning piglets. A total of 16 piglets from 8 litters were used in the experiment. One group of piglets was nursed by sows until age 21 days, and another group was weaned at age 14 days and then fed creep feed instead of breast milk for 7 days. Piglets were killed at 21 days, and the jejunum segments were dissected. After sequential isolation of jejunum epithelial cells along the crypt-villus axis, their proteins were analyzed through the isobaric tags for relative and absolute quantification, and proteins involved in the mammalian target of rapamycin signaling pathway and proliferating cell nuclear antigen abundances in jejunal epithelial cells of weaning or suckling group were determined by Western blotting. The differential proteins in three cell fractions were identified and analyzed. The results showed that proteins involved in the tricarboxylic acid cycle, β-oxidation, and the glycolysis pathway were significantly downregulated in the upper and middle villus of the early-weaned group. However, proteins involved in glycolysis were significantly upregulated in crypt cells. In addition, Western blot analysis showed that the expression of mammalian target of rapamycin pathway-related proteins was decreased (P early-weaned group. The present results showed that early-weaning differentially affect the expression of proteins involved in energy production of enterocytes along the jejunal crypt-villus axis. Copyright © 2015 the American Physiological Society.

  16. Temozolomide increases the number of mismatch repair-deficient intestinal crypts and accelerates tumorigenesis in a mouse model of Lynch syndrome.

    Science.gov (United States)

    Wojciechowicz, Kamila; Cantelli, Erika; Van Gerwen, Bastiaan; Plug, Mirjam; Van Der Wal, Anja; Delzenne-Goette, Elly; Song, Ji-Ying; De Vries, Sandra; Dekker, Marleen; Te Riele, Hein

    2014-11-01

    Lynch syndrome, a nonpolyposis form of hereditary colorectal cancer, is caused by inherited defects in DNA mismatch repair (MMR) genes. Most patients carry a germline mutation in 1 allele of the MMR genes MSH2 or MLH1. With spontaneous loss of the wild-type allele, cells with defects in MMR exist among MMR-proficient cells, as observed in healthy intestinal tissues from patients with Lynch syndrome. We aimed to create a mouse model of this situation to aid in identification of environmental factors that affect MMR-defective cells and their propensity for oncogenic transformation. We created mice in which the MMR gene Msh2 can be inactivated in a defined fraction of crypt base columnar stem cells to generate MSH2-deficient intestinal crypts among an excess of wild-type crypts (Lgr5-CreERT2;Msh2(flox/-) mice). Intestinal tissues were collected; immunohistochemical analyses were performed for MSH2, along with allele-specific PCR assays. We traced the fate of MSH2-deficient crypts under the influence of different external factors. Lgr5-CreERT2;Msh2(flox/-) mice developed more adenomas and adenocarcinomas than control mice; all tumors were MSH2 deficient. Exposure of Lgr5-CreERT2;Msh2(flox/-) mice to the methylating agent temozolomide caused MSH2-deficient intestinal stem cells to proliferate more rapidly than wild-type stem cells. The MSH2-deficient intestinal stem cells were able to colonize the intestinal epithelium and many underwent oncogenic transformation, forming intestinal neoplasias. We developed a mouse model of Lynch syndrome (Lgr5-CreERT2;Msh2(flox/-) mice) and found that environmental factors can modify the number and mutability of the MMR-deficient stem cells. These findings provide evidence that environmental factors can promote development of neoplasias and tumors in patients with Lynch syndrome. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Cryosectioning the intestinal crypt-villus axis: An ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells

    OpenAIRE

    Vincent, Audrey; Kazmierczak, Catherine; Duchêne, Belinda; Jonckheere, Nicolas; Leteurtre, Emmanuelle; Seuningen, Isabelle Van

    2015-01-01

    The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone...

  18. [Influence of age on optical aberrations of the human eye].

    Science.gov (United States)

    Jahnke, M; Wirbelauer, C; Pham, D T

    2006-07-01

    Currently the influence of age on corneal and ocular aberrations is still insufficiently known. The aim of this clinical study was to compare age-related aberrations of human eyes. In a prospective study 98 eyes of 49 healthy patients ranging from 17 to 65 years of age (38.6+/-10.0 years) were consecutively examined. The best corrected visual acuity ranged from 0.8 to 1.6; 48 eyes were emmetropic (SE+/-0.5 D), 42 eyes myopic (SE +0.5 to +3.88 D). The corneal aberrations were derived from corneal topography (Keratron Scout, Optikon). The measurement of ocular aberrations was performed with a Tscherning wavefront aberrometer (ORK, Schwind). The aberrations of the Zernike coefficients and RMS values (1st to 4th order) were determined. The mean corneal and ocular Zernike coefficients of higher order were smaller than 0.2 microm. There was an evident decrease of wavefront aberrations with increasing order. Higher order corneal aberrations were larger than the corresponding ocular aberrations. With increasing age higher optical errors increased in complexity, and the correlation of corneal and ocular aberrations decreased with significant differences. Although the corneal ocular RMS value of the 3rd and 4th order correlated in the younger group (r=0.51, p=0.0001), there was no correlation in the older group (r=-0.48, p=0.832). The influence of age caused a significant increase of ocular aberrations of the 3rd and 4th order, in particular a tenfold extension of coma (C07) (p=0.002), a twofold extension of spherical aberration (C12) (p=0.0001), and an increase of the 3rd and 4th order RMS values (p=0.001). Increased age induced an increase in optical aberrations of the eye, which demonstrates the influence of the lens on ocular aberrations. The combination of corneal and ocular diagnostic methods is recommendable for a better understanding of visual performance.

  19. Electroencephalogram in attention deficit hyperactivity disorder: spike and wave paroxysms, foci, and seizures.

    Science.gov (United States)

    Altunel, Attila; Altunel, Emine Özlem; Sever, Ali

    2013-08-01

    Attention deficit hyperactivity disorder is a syndrome of unknown etiology that affects 3% to 7% of the population. Although no objective test exists to support the diagnosis, EEG discharges related to the neuropsychiatric abnormalities have a high incidence in attention deficit hyperactivity disorder. The aim of this study was to elucidate the quantitative and qualitative characteristics of EEG abnormality in attention deficit hyperactivity disorder. Nonrapid eye movement sleep EEGs were evaluated in 134 patients with attention deficit hyperactivity disorder in terms of age, EEG timing, spike and wave index, foci, and seizures. All patients had spike and wave paroxysms that changed with age at and time to first EEG. Only half of the patients had seizures and 46 patients had neither seizures nor foci. Thirty-eight patients had the EEG findings of benign focal epilepsy of childhood. Our data support the view that spike and wave activity evolves in time and that EEG discharges are related to neuropsychiatric symptoms even when a diagnosable seizure disorder is absent.

  20. Characteristics of {gamma}-H2AX foci at DNA double-strand breaks sites

    Energy Technology Data Exchange (ETDEWEB)

    Pilch, D.R.; Sedelnikova, O.A.; Redon, C. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States); Celeste, A.; Nussenzweig, A. [National Cancer Institute, National Institutes of Health, Experimental Immunology Branch, Bethesda, Maryland (United States); Bonner, W.M. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States)

    2003-06-01

    Phosphorylated H2AX ({gamma}-H2AX) is essential to the efficient recognition and (or) repair of DNA double strand breaks (DSBs), and many molecules, often thousands, of H2AX become rapidly phosphorylated at the site of each nascent DSB. An antibody to {gamma}-H2AX reveals that this highly amplified process generates nuclear foci. The phosphorylation site is a serine four residues from the C-terminus which has been evolutionarily conserved in organisms from giardia intestinalis to humans. Mice and yeast lacking the conserved serine residue demonstrate a variety of defects in DNA DSB processing. H2AX{sup {delta}}{sup /{delta}} mice are smaller, sensitive to ionizing radiation, defective in class switch recombination and spermatogenesis while cells from the mice demonstrate substantially increased numbers of genomic defects. {gamma}-H2AX foci formation is a sensitive biological dosimeter and presents new and exciting opportunities to understand important biological processes, human diseases, and individual variations in radiation sensitivity. These potentialities demonstrate the importance of understanding the parameters and functions of {gamma}-H2AX formation. (author)

  1. A review of spatial computational models for multi-cellular systems, with regard to intestinal crypts and colorectal cancer development.

    Science.gov (United States)

    De Matteis, Giovanni; Graudenzi, Alex; Antoniotti, Marco

    2013-06-01

    Colon rectal cancers (CRC) are the result of sequences of mutations which lead the intestinal tissue to develop in a carcinoma following a "progression" of observable phenotypes. The actual modeling and simulation of the key biological structures involved in this process is of interest to biologists and physicians and, at the same time, it poses significant challenges from the mathematics and computer science viewpoints. In this report we give an overview of some mathematical models for cell sorting (a basic phenomenon that underlies several dynamical processes in an organism), intestinal crypt dynamics and related problems and open questions. In particular, major attention is devoted to the survey of so-called in-lattice (or grid) models and off-lattice (off-grid) models. The current work is the groundwork for future research on semi-automated hypotheses formation and testing about the behavior of the various actors taking part in the adenoma-carcinoma progression, from regulatory processes to cell-cell signaling pathways.

  2. Higher-Order Wavefront Aberrations for Populations of Young Emmetropes and Myopes

    Directory of Open Access Journals (Sweden)

    Jinhua Bao

    2009-01-01

    Conclusions: Human eyes have systematical higher order aberrations in population, and factors that cause bilateral symmetry of wavefront aberrations between the right and left eyes made important contribution to the systematical aberrations.

  3. Imaging and clinical characteristics of children with multiple foci of microsusceptibility changes in the brain on susceptibility-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Aida, Noriko; Fujita, Kazutoshi; Shishikura, Ayako [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Takahara, Taro; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Miyata, Daiki [Kanagawa Children' s Medical Center, Department of Circulation Medicine, Yokohama (Japan); Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2010-10-15

    Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT (n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss (n = 5), delayed myelination (n = 2), acute infarction (n = 1), chronic infarction (n = 1), meningitis (n = 1), slight signal abnormality in the white matter (n = 1) and no abnormal findings (n = 1). Follow-up SWI (n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. (orig.)

  4. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    Science.gov (United States)

    Rafelski, Susanne M.; Keller, Lani C.; Alberts, Jonathan B.; Marshall, Wallace F.

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  5. The Mechanisms of Aberrant Protein Aggregation

    Science.gov (United States)

    Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

    2012-02-01

    We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

  6. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  7. Broadband aberration-free focusing reflector for acoustic waves

    Science.gov (United States)

    Wang, Aixia; Qu, Shaobo; Ma, Hua; Wang, Jiafu; Jiang, Wei; Feng, Mingde

    2017-11-01

    An aberration-free focusing reflector (AFR) for acoustic waves is proposed with the aim to eliminate spherical aberration and coma simultaneously. Meanwhile, the AFR can focus acoustic waves with low dispersion in a wide frequency range of 14-50 kHz. The broadband aberration-free focusing effect is originated from an elliptical reflection phase gradient profile, which is achieved by milling different depths of axisymmetric grooves on a planoconcave-like brass plate using the ray theory. Theoretical and numerical results are in good agreement. The designed AFR can find broad engineering, industrial and medical applications.

  8. Simple numerical chromosome aberrations in two pituitary adenomas

    DEFF Research Database (Denmark)

    Dietrich, C U; Pandis, N; Bjerre, P

    1993-01-01

    -secreting adenoma, three aberrant clones were detected, giving the karyotype 45,X, -Y[20]/47,XY, +Y[6]/45,XY, -21[3]/46,XY[21]. One cell had the chromosome complement 46,X, -Y, +9; no other nonclonal aberrations were detected. The only hitherto published case of pituitary adenoma analyzed by banding techniques (Rey...... et al. [1986]: Cancer Genet Cytogenet 23:171-174) also had only numerical clonal changes that included extra copies of chromosome 9. We conclude that pituitary adenomas may be karyotypically characterized by numerical aberrations and that trisomy 9 seems to be the best candidate for a primary...

  9. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.

    2015-01-01

    chromosomal structural rearrangements and single nucleotide variants (SNVs). Conventional AML diagnostics and recent seminal next-generation sequencing (NGS) studies have identified more than 200 recurrent genetic aberrations presenting in various combinations in individual patients. Significantly, many...... of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal...

  10. Aberrations of Genetic Material as Biomarkers of Ionizing Radiation Effects

    Energy Technology Data Exchange (ETDEWEB)

    Milacic, S.

    2004-07-01

    Ionizing radiation is the most powerful mutagen in environmental and working conditions. The result of genotoxic effect of radiation is the development of chromosome aberrations. The structural chromosome aberrations in peripheral blood lymphocytes are dicentric, ring, acentric fragment. The observation of chromosome aberration frequency in lymphocyte karyotype is the conclusive method to assess the absorbed dose of ionizing radiation. Our study compared the incidence of chromosome aberrations in occupationally exposed healthy medical workers and in non-exposed healthy population. We analyzed the effect of working place, dose by thermo luminescence personal dosimeter (TLD), duration of occupational exposure (DOE) and age to the sum of aberrant cells and aberrations. four-year study included 462 subjects, mean-aged 42.3 years, who were occupational exposed to ionizing radiation and 95 subjects, mean-aged 35,2 years, who were not exposed to ionizing radiation, during the same time period and from the same territory. All of them possess thermo luminescence personal dosimeter (TLD) which is read by scanner for thermo luminescence dosimeters. Modified Moorheard's micro method for peripheral blood lymphocytes and conventional cytogenetic technique of chromosome aberration analysis were used for analysis of chromosome aberrations. Stained preparations (Giemsa) are observed in immersion by light microscope. The karyotype of 200 lymphocytes in metaphase is analyzed the most characteristic aberration: dicentric, then the ring and acentric fragments. The increased incidence of chromosome aberrations was found to tbe 21.6% in the exposed group and 2.1% in the controls, while the findings within the limits (non-specific chromosome lesions-gaps breaks, elongations, and exchanges) were equal in both groups (22%). Among occupationally exposed medical workers, the highest incidence was found in nuclear medicine workers (42.6%), then in orthopedists (27.08%). There is highly

  11. Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

    OpenAIRE

    Ho, Ket Li; Chong, Pei Pei; Yazan, Latifah Saiful; Ismail, Maznah

    2012-01-01

    Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rat...

  12. gammaH2AX foci form preferentially in euchromatin after ionising-radiation.

    Directory of Open Access Journals (Sweden)

    Ian G Cowell

    Full Text Available BACKGROUND: The histone variant histone H2A.X comprises up to 25% of the H2A complement in mammalian cells. It is rapidly phosphorylated following exposure of cells to double-strand break (DSB inducing agents such as ionising radiation. Within minutes of DSB generation, H2AX molecules are phosphorylated in large chromatin domains flanking DNA double-strand breaks (DSBs; these domains can be observed by immunofluorescence microscopy and are termed gammaH2AX foci. H2AX phosphorylation is believed to have a role mounting an efficient cellular response to DNA damage. Theoretical considerations suggest an essentially random chromosomal distribution of X-ray induced DSBs, and experimental evidence does not consistently indicate otherwise. However, we observed an apparently uneven distribution of gammaH2AX foci following X-irradiation with regions of the nucleus devoid of foci. METHODOLOGY/PRINCIPLE FINDINGS: Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation. H2AX phosphorylation has also been demonstrated previously to occur at stalled replication forks induced by UV radiation or exposure to agents such as hydroxyurea. In this study, treatment of S-phase cells with hydroxyurea lead to efficient H2AX phosphorylation in both euchromatin and heterochromatin at times when these chromatin compartments were undergoing replication. This suggests a block to H2AX phosphorylation in heterochromatin that is at least partially relieved by ongoing DNA replication. CONCLUSIONS/SIGNIFICANCE: We discuss a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since gammaH2AX is regarded as forming a platform for the recruitment or retention of other DNA repair and signaling molecules, these findings imply that the processing of DSBs in heterochromatin differs from that in euchromatic regions. The

  13. ON STRUCTURED AND DIFFUSE SEISMICITY, STIFFNESS OF EARTHQUAKE FOCI, AND NONLINEARITY OF MAGNITUDE RECURRENCE GRAPHS

    Directory of Open Access Journals (Sweden)

    Evgeny G. Bugaev

    2015-09-01

    Full Text Available Geological, geophysical and seismogeological studies are now conducted in a more detail and thus provide for determining seismic sources with higher accuracy, from the first meters to first dozens of meters [Waldhauser, Schaff, 2008]. It is now possible to consider uncertainty ellipses of earthquake hypocenters, that are recorded in the updated Earthquake Catalogue, as surfaces of earthquake focus generators. In our article, it is accepted that a maximum horizontal size of an uncertainty ellipse corresponds to an area of a focus generator, and seismic events are thus classified into two groups, earthquakes with nonstiff and stiff foci. Criteria of such a classification are two limits of elastic strain and brittle strain in case of uniaxial (3⋅10–5 or omnidirectional (10–6 compression. The criteria are established from results of analyses of parameters of seismic dislocations and earthquake foci with regard to studies of surface parameters and deformation parameters of fault zones. It is recommendable that the uniaxial compression criterion shall be applied to zones of interaction between tectonic plates, and the unilateral compression criterion shall be applied to low active (interplate areas. Sample cases demonstrate the use of data sets on nonstiff and stiff foci for separate evaluation of magnitude reoccurrence curves, analyses of structured and dissipated seismicity, review of the physical nature of nonlinearity of recurrence curves and conditions of preparation of strong earthquakes. Changes of parameters of the recurrence curves with changes of data collection square areas are considered. Reviewed are changes of parameters of the recurrence curves during preparation for the Japan major earthquake of 11 March 2011 prior to and after the major shock. It is emphasized that it is important to conduct even more detailed geological and geophysical studies and to improve precision and sensitivity of local seismological monitoring networks

  14. Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

    Science.gov (United States)

    Callegaro, Giulia; Corvi, Raffaella; Salovaara, Susan; Urani, Chiara; Stefanini, Federico M

    2017-06-01

    Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Live Dynamics of 53BP1 Foci Following Simultaneous Induction of Clustered and Dispersed DNA Damage in U2OS Cells.

    Science.gov (United States)

    Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Scherthan, Harry; Wojcik, Andrzej

    2018-02-08

    Cells react differently to clustered and dispersed DNA double strand breaks (DSB). Little is known about the initial reaction to simultaneous induction of DSBs with different complexities. Here, we used live cell microscopy to analyse the behaviour of 53BP1-GFP (green fluorescence protein) foci formation at DSBs induced in U2OS cells by alpha particles, X-rays or mixed beams over a 75 min period post irradiation. X-ray-induced foci rapidly increased and declined over the observation interval. After an initial increase, mixed beam-induced foci remained at a constant level over the observation interval, similarly as alpha-induced foci. The average areas of radiation-induced foci were similar for mixed beams and X-rays, being significantly smaller than those induced by alpha particles. Pixel intensities were highest for mixed beam-induced foci and showed the lowest level of variability over time as compared to foci induced by alphas and X-rays alone. Finally, mixed beam-exposed foci showed the lowest level of mobility as compared to alpha and X-ray exposure. The results suggest paralysation of chromatin around foci containing clustered DNA damage.

  16. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  17. Early Development of Children with Sex Chromosome Aberrations.

    Science.gov (United States)

    Haka-Ilse, Katerina; And Others

    1978-01-01

    Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A prospective study was made of the early development of 42 children with sex chromosome aberrations. (Author)

  18. Impact of primary aberrations on coherent lidar performance

    DEFF Research Database (Denmark)

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist

    2014-01-01

    In this work we investigate the performance of a monostatic coherent lidar system in which the transmit beam is under the influence of primary phase aberrations: spherical aberration (SA) and astigmatism. The experimental investigation is realized by probing the spatial weighting function...... of the lidar system using different optical transceiver configurations. A rotating belt is used as a hard target. Our study shows that the lidar weighting function suffers from both spatial broadening and shift in peak position in the presence of aberration. It is to our knowledge the first experimental...... demonstration of these tendencies. Furthermore, our numerical and experimental results show good agreement. We also demonstrate how the truncation of the transmit beam affects the system performance. It is both experimentally and numerically proven that aberration effects have profound impact on the antenna...

  19. Chromosome aberrations in pesticide-exposed greenhouse workers

    DEFF Research Database (Denmark)

    Lander, B F; Knudsen, Lisbeth E.; Gamborg, M O

    2000-01-01

    OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116...... greenhouse workers exposed to a complex mixture of almost 50 insecticides, fungicides, and growth regulators and also for 29 nonsmoking, nonpesticide-exposed referents. RESULTS: The preseason frequencies of chromosome aberrations were slightly but not statistically significantly elevated for the greenhouse...... workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding...

  20. Aberrant internal carotid artery in the middle ear

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Keun Tak; Kang, Hyun Koo [Dept. of Radiology, Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2014-10-15

    The knowledge about the aberrant internal carotid artery (ICA) in the middle ear is essential for clinicians, because a misdiagnosis of the aberrant ICA could have serious consequences such as excessive aural bleeding during a middle ear surgery. A 38-year-old woman presented with tinnitus and hearing difficulties of the left ear that had started 5 years ago. During otoscopy, an anteroinferior bluish mass was seen in the tympanic space. Computed tomography and magnetic resonance imaging demonstrated a left-side aberrant ICA with bony dehiscence of the carotid canal in the middle ear and a reduced diameter of the tympanic ICA. Herein we report a case of an aberrant ICA in the middle ear. We also review the literature regarding this important vascular anomaly of the temporal bone which may lead to disastrous surgical complications.

  1. Not Always Black and White: Colour Aberrations in the Dovekie

    National Research Council Canada - National Science Library

    DARIUSZ JAKUBAS; KATARZYNA WOJCZULANIS-JAKUBAS

    2012-01-01

    We describe four records of colour aberrations in the dovekie (Alle alle). During six years of studies of breeding ecology in two large dovekie colonies in West Spitsbergen, we recorded one albino chick...

  2. Are persistent delusions in schizophrenia associated with aberrant salience?

    Directory of Open Access Journals (Sweden)

    Rafeef Abboud

    2016-06-01

    Conclusion: These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.

  3. [Cystic dystrophy on aberrant pancreas. Contribution of ultrasound-endoscopy].

    Science.gov (United States)

    Andrieu, J; Palazzo, L; Chikli, F; Doll, J; Chome, J

    1989-06-01

    Cystic dystrophy of aberrant pancreatic tissue without chronic pancreatitis is a rare disease described by Potet and Duclert in 1970. Clinical diagnosis is possible by endoscopy and intraluminalsonography; we report the first case diagnosed by intraluminalsonography.

  4. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    George S. Karagiannis

    2011-01-01

    Full Text Available An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomyosis, and cystic endometrial hyperplasia. Interestingly, such combination was never encountered before in dogs. Although uterine leiomyoma is quite usual in the reproductive system of female dogs, this case resembled relevant cases of human uterine adenomyomas in morphology, and thus it was offered a similar tentative diagnosis.

  5. Multistability in Chua's circuit with two stable node-foci

    Energy Technology Data Exchange (ETDEWEB)

    Bao, B. C.; Wang, N.; Xu, Q. [School of Information Science and Engineering, Changzhou University, Changzhou 213164 (China); Li, Q. D. [Research Center of Analysis and Control for Complex Systems, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China)

    2016-04-15

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponent spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.

  6. Immunofluorescence detection of clustered gamma-H2AX foci induced by HZE-particle radiation.

    Science.gov (United States)

    Desai, N; Davis, E; O'Neill, P; Durante, M; Cucinotta, F A; Wu, H

    2005-10-01

    We studied the spatial and temporal distributions of foci of the phosphorylated form of the histone protein H2AX (gamma-H2AX), which is known to be activated by double-strand breaks after irradiation of human fibroblast cells with high-energy silicon (54 keV/microm) and iron (176 keV/microm) ions. Here we present data obtained with the ion path parallel to a monolayer of human fibroblast cells that leads to gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in an x/y plane, thus enabling the analysis of the fluorescence distributions along the ion trajectories. Qualitative analyses of these distributions provide insights into DNA damage processing kinetics for high charge and energy (HZE) ions, including evidence of increased clustering of DNA damage and slower processing with increasing LET.

  7. Prevalence of small testicular hyperechogenic foci in subgroups of 382 non-vasectomized, azoospermic men

    DEFF Research Database (Denmark)

    Fedder, Jens

    2017-01-01

    Testicular hyperechogenic foci (THF) are associated with Klinefelter’s syndrome, cryptorchidism, infertility, and testicular germ cell neoplasia. The aims of the study were to evaluate THF in relation to etiology of azoospermia and to Sertoli cell dysfunction. The structures inside the scrotum...... technique for detection of cytokeratin-18 (CK-18). The prevalence of THF was 13.4%. uTHF was found in 11 men (2.9%), the pattern was bilateral in four while other four had bTHF in the other testis. pTHF was detected in eight cases (2.1%), and except for one case with Klinefelter’s syndrome, pTHF was in all...

  8. Hepatocellular Carcinoma in Noncirrhotic Liver with Glycogenotic Foci: Basic Science Meets Genomic Medicine.

    Science.gov (United States)

    Lefkowitch, Jay H; Lagana, Stephen M; Kato, Tomoaki

    2015-11-01

    During the past decade, the application of genomic analysis to liver tumors has provided extensive data concerning tumor phenotypes, signatures, outcomes, and prognosis. In this report the authors describe a middle-aged man without known risk factors for liver disease or hepatocellular carcinoma (HCC) who developed a 19-cm HCC in his right lobe. The underlying liver was normal histologically except for multifocal glycogenotic foci similar to those found in experimental chemical carcinogenesis. Precision genomic analysis of this tumor disclosed five alterations with amplifications of genes CCNE1, FGF3 and FGF4, MYCL1, and ARID1A. The roles of these gene mutations and their potential effects in carcinogenesis in this case are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-10-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  10. Image-Based High Content Screening: Automating the Quantification Process for DNA Damage-Induced Foci.

    Science.gov (United States)

    Lim, Yi Chieh

    2017-01-01

    Visual inspection of cellular activities based on conventional fluorescence microscope is a fundamental tool to study the role of DNA damage response (DDR). In the context of drug discovery where the capture of thousands of images is required across parallel experiments, this presents a challenge to data collection and analysis. Manual scoring is laborious and often reliant on trained personnel to intuit biological meaning through visual reasoning. On the other hand, high content screening combines the automation of microscopy image acquisition and analysis in a single platform to quantify cellular events of interests. The data generated is rapid and accurate, lessening the bias of human interpretation. Herein, this chapter will describe an image-based high content screen approach and the data analysis of Ataxia-Telangiectasia Mutated (ATM) DNA damage-induced foci.

  11. A Study of Appendiceal Crypt Cell Adenocarcinoma (So-Called Goblet Cell Carcinoid and Its Related Adenocarcinoma).

    Science.gov (United States)

    Nonaka, Daisuke; Papaxoinis, George; Lamarca, Angela; Fulford, Paul; Valle, Juan; Chakrabarty, Bipasha

    2017-08-17

    Goblet cell carcinoids (GCCs) of the appendix are rare tumors, characterized by a carcinoid-like organoid growth pattern. Despite the term carcinoid, neuroendocrine features are inconspicuous, and its behavior is distinct from carcinoid. Its high grade counterpart is designated as adenocarcinoma ex GCC. We conducted a retrospective study of 105 tumors to find prognostic values of a variety of clinico-pathologic features. The tumors were subclassified as low grade, equivalent to classic type, and high grade, defined as loss of organoid pattern, and a proportion (%) of low and high grades were documented in each tumor. Correlations between survival and various clinico-pathologic parameters were investigated. One-third were pure low grade while the remainder contained variable high grade component ranging 5-95%. Neuroendocrine cell component ranged 0-90% (median 5) while mucus cell component ranged 5-100% (median 70). By univariate analysis, size, stage, high grade component, nuclear grade, surgery and chemotherapy correlated with cancer-related survival (CSS), and by multivariate analysis, stage (P=.001), high grade component (P=.008) and tumor size (P=.005) correlated with CSS. There was significant difference in CSS when the cases were grouped in high grade component <40%, 40-90 and ≤90% (P<.001). Our results indicate that staging and proportion of high grade histology may provide important prognostic information. Neuroendocrine component was insignificant in both low and high grade areas. In light of our findings, this tumor type is best regarded as a variant of adenocarcinoma, and the term crypt cell adenocarcinoma more appropriately reflects the nature and origin of this tumor group. Copyright © 2017. Published by Elsevier Inc.

  12. The Viral Mimetic Polyinosinic:Polycytidylic Acid Alters the Growth Characteristics of Small Intestinal and Colonic Crypt Cultures.

    Directory of Open Access Journals (Sweden)

    Julie M Davies

    Full Text Available The intestinal epithelium is the first line of defense against enteric pathogens. We investigated the response of small intestinal and colonic crypt cultures to a panel of toll-like receptor ligands to assess the impact of microbial pattern recognition on epithelial growth.Primary murine jejunal enteroids and colonoids were cultured with lipopeptide Pam3CSK4, lipopolysaccharide (LPS or polyinosinic:polycytidylic acid (Poly I:C for 4 to 6 days. Surface area, budding and survival were assessed. Proliferation and numbers of lysozyme positive cells were quantified by flow cytometry. Gene expression was assessed by Nanostring and qRT-PCR.Exposure to Pam3CSK4 and LPS had minimal impact on either enteroids or colonoids. In contrast, Poly I:C increased the surface area of enteroids, while colonoids demonstrated decreased budding. Survival was decreased by Poly I:C in enteroids but not in colonoids. Both enteroids and colonoids exhibited upregulated gene expression of chemokines, but these were increased in magnitude in enteroids. Decreases in gene expression associated with epithelial differentiation and lysozyme positive cells were more apparent in enteroids than in colonoids. Baseline gene expression between enteroids and colonoids differed markedly in levels of stem cell and inflammatory markers. The changes in morphology induced by Poly I:C were mediated by the toll-like receptor adaptor molecule 1 (Ticam1 in enteroids but not in colonoids.Poly I:C alters the molecular program of epithelial cells and shifts from absorption and digestion towards defense and inflammation. Diversity of responses to microbial patterns in enteroids and colonoids may underlie differences in susceptibility to infection along the intestinal tract.

  13. Corneal aberrations before and after small-incision cataract surgery.

    Science.gov (United States)

    Guirao, Antonio; Tejedor, Jaime; Artal, Pablo

    2004-12-01

    To study the effect of small-incision cataract surgery on the optical aberrations of the cornea. Corneal topography was measured before and after cataract surgery on 70 eyes of 70 patients. Monofocal foldable IOLs were implanted after phacoemulsification through a clear-cornea, 3.5-mm incision without suture. Corneal aberrations, up to the fifth order and 6-mm pupil, were calculated by ray-tracing from the corneal topography. Pre- and postoperative aberrations were compared in each patient and the optical changes induced by surgery investigated. The root mean square of the wave aberration slightly increased on average after surgery (pre, 0.65 +/- 0.46 microm; post, 0.85 +/- 0.63 microm). Most aberration terms were similar, averaged across the 70 patients, before and after surgery (spherical aberration: pre, 0.32 +/- 0.12 microm, and post, 0.34 +/- 0.19 microm; astigmatism: pre, 0.9 +/- 0.8 D, and post, 1.1 +/- 1.0 D; coma: pre, 0.27 +/- 0.18 microm, and post, 0.32 +/- 0.33 microm). However, in each patient, there were changes after surgery in the magnitude (either increasing or decreasing) and/or orientation of aberrations. The mean induced astigmatism was -1.0 +/- 0.9 D at the orientation of the surgical meridian. Induced trefoil also showed a predominant pattern at this direction. Patients with nasal incisions experienced larger changes. Small-incision surgery does not systematically degrade the optical quality of the anterior corneal surface. However, it introduces changes in some aberrations, especially in nonrotationally symmetric terms such as astigmatism, coma, and trefoil. The incision site plays a main role in the corneal changes after surgery.

  14. Modified matching Ronchi test to visualize lens aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Hassani, Kh; Ziafi, H Hooshmand, E-mail: hassanikh@ut.ac.ir [Optics Research Lab 3, Department of Physics, University of Tehran, PO Box 14395/547, Tehran (Iran, Islamic Republic of)

    2011-09-15

    We introduce a modification to the matching Ronchi test to visualize lens aberrations with simple and inexpensive equipment available in educational optics labs. This method can help instructors and students to observe and estimate lens aberrations in real time. It is also a semi-quantitative tool for primary tests in research labs. In this work by comparing a single lens with a doublet, we can clearly demonstrate the superior quality of the doublet over the single lens, and estimate their conic constants.

  15. The Adequacy of the Q Methodology for Clinical Validation of Nursing Diagnoses Related to Subjective Foci.

    Science.gov (United States)

    Miguel, Susana; Caldeira, Sílvia; Vieira, Margarida

    2016-11-17

    This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. Discussion paper about the characteristics of the Q methodology. This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. © 2016 NANDA International, Inc.

  16. [Alternatives to femtosecond laser technology: subnanosecond UV pulse and ring foci for creation of LASIK flaps].

    Science.gov (United States)

    Vogel, A; Freidank, S; Linz, N

    2014-06-01

    In refractive corneal surgery femtosecond (fs) lasers are used for creating LASIK flaps, dissecting lenticules and for astigmatism correction by limbal incisions. Femtosecond laser systems are complex and expensive and cutting precision is compromised by the large focal length associated with the commonly used infrared (IR) wavelengths. Based on investigations of the cutting dynamics, novel approaches for corneal dissection using ultraviolet A (UVA) picosecond (ps) pulses and ring foci from vortex beams are presented. Laser-induced bubble formation in corneal stroma was investigated by high-speed photography at 1-50 million frames/s. Using Gaussian and vortex beams of UVA pulses with durations between 200 and 850 ps the laser energy needed for easy removal of flaps created in porcine corneas was determined and the quality of the cuts by scanning electron microscopy was documented. Cutting parameters for 850 ps are reported also for rabbit eyes. The UV-induced and mechanical stress were evaluated for Gaussian and vortex beams. The results show that UVA picosecond lasers provide better cutting precision than IR femtosecond lasers, with similar processing times. Cutting energy decreases by >50 % when the laser pulse duration is reduced to 200 ps. Vortex beams produce a short, donut-shaped focus allowing efficient and precise dissection along the corneal lamellae which results in a dramatic reduction of the absorbed energy needed for cutting and of mechanical side effects as well as in less bubble formation in the cutting plane. A combination of novel approaches for corneal dissection provides the option to replace femtosecond lasers by compact UVA microchip laser technology. Ring foci are also of interest for femtosecond laser surgery, especially for improved lenticule excision.

  17. Generalized Alvarez lens for correction of laser aberrations

    Energy Technology Data Exchange (ETDEWEB)

    LaFortune, K N

    2004-12-02

    The Alvarez lens (US Patent No. 3,305,294 [1]) is a compact aberration corrector. The original design emphasized in the patent consists of a pair of adjacent optical elements that provide a variable focus. A lens system with a variable effective focal length is nothing new. Such systems are widely used in cameras, for example. It is the compactness and simplicity of operation that is the key advantage of the Alvarez lens. All of the complexity is folded into the design and fabrication of the optical elements. As mentioned in the Alvarez patent [1] and elaborated upon in Palusinski et al. [2], if one is willing to fold even more complexity into the optical elements, it is possible to correct higher-order aberrations as well. There is no theoretical limit to the number or degree of wavefront distortions that can be corrected. The only limitation is that there must be a fixed relative magnitude of the aberrations. Independent correction of each component of the higher-order aberrations can not be performed without additional elements and degrees of freedom [3]. Under some circumstances, coupling may be observed between different aberrations. This can be mitigated with the appropriate choice of design parameters. New methods are available today that increase the practicality of making higher-order aberration correctors [4,5,6].

  18. Transcranial phase aberration correction using beam simulations and MR-ARFI

    Energy Technology Data Exchange (ETDEWEB)

    Vyas, Urvi, E-mail: urvi.vyas@gmail.com; Kaye, Elena; Pauly, Kim Butts [Department of Radiology, Stanford University, Stanford, California 94305 (United States)

    2014-03-15

    Purpose: Transcranial magnetic resonance-guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation-MR-ARFI technique to achieve aberration correction for transcranial MR-guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR-ARFI) to correct skull-caused phase aberrations. Methods: Skull-based numerical aberrations were obtained from a MR-guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focused ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR-ARFI images were used in the hybrid simulation-MR-ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16-aberration and 1024-aberration) was repeated three times. Results: The corrected MR-ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation-MR-ARFI technique resulted in an average increase in focal MR-ARFI phase of 44% for the 16-aberration case and 52% for the 1024-aberration case, and recovered 83% and 39% of the ideal MR-ARFI phase for the 16-aberrations and 1024-aberration case, respectively. Conclusions: Using one MR-ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation-MR-ARFI technique improved the maximum MR-ARFI phase of the beam's focus.

  19. Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, Hiroshi [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Fujimori, Akira [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Uesaka, Mitsuru [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Yajima, Hirohiko, E-mail: hyajima@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2015-01-15

    Highlights: • CtIP becomes hyperphosphorylated and forms foci following cell irradiation. • CtIP accumulates in foci subsequent to the peak of hyperphosphorylation. • CtIP is maintained in a hypophosphorylated state at later times. • CtIP is continuously recruited to DNA double strand breaks downstream of resection. • CtIP presumably have a distinct role following the initiation of resection. - Abstract: Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3′-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs. At early times following exposure of human cells to ionizing radiation, CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM-dependent manner. At later times, when the initiation of resection had occurred, CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over at DSB sites downstream of resection. Our findings provide strong evidence that CtIP is continuously recruited to DSBs downstream of both the initiation and extension step of resection, strongly suggesting that CtIP has functions in addition to promoting the initiation of resection during HR.

  20. AFSC/RACE/EcoFOCI: 2011 Gulf of Alaska Late Larval Survey DY11-02/2DY11

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A total of 70 stations were occupied. The standard FOCI grid and line 8 were samped. At each station we sampled using paired 20 and 60 cm Bongo frames (150 and 500...

  1. Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

    Directory of Open Access Journals (Sweden)

    Youn-Bok Lee

    2013-12-01

    Full Text Available The GGGGCC (G4C2 intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  2. Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.

    Science.gov (United States)

    Mori, Kiyoshi; Takeda, Masashi; Kodama, Yoshinori; Kiyokawa, Hiroki; Yasojima, Hiroyuki; Mizutani, Makiko; Otani, Yoko; Morikawa, Nozomi; Masuda, Norikazu; Mano, Masayuki

    2017-06-01

    Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Sommersdorf mummies—An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany

    Science.gov (United States)

    Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

    2017-01-01

    Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle’s church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases. PMID:28859116

  4. The Sommersdorf mummies-An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany.

    Directory of Open Access Journals (Sweden)

    Amelie Alterauge

    Full Text Available Sommersdorf Castle (Bavaria, Germany is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle's church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT, was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases.

  5. Volumetric optical coherence microscopy enabled by aberrated optics (Conference Presentation)

    Science.gov (United States)

    Mulligan, Jeffrey A.; Liu, Siyang; Adie, Steven G.

    2017-02-01

    Optical coherence microscopy (OCM) is an interferometric imaging technique that enables high resolution, non-invasive imaging of 3D cell cultures and biological tissues. Volumetric imaging with OCM suffers a trade-off between high transverse resolution and poor depth-of-field resulting from defocus, optical aberrations, and reduced signal collection away from the focal plane. While defocus and aberrations can be compensated with computational methods such as interferometric synthetic aperture microscopy (ISAM) or computational adaptive optics (CAO), reduced signal collection must be physically addressed through optical hardware. Axial scanning of the focus is one approach, but comes at the cost of longer acquisition times, larger datasets, and greater image reconstruction times. Given the capabilities of CAO to compensate for general phase aberrations, we present an alternative method to address the signal collection problem without axial scanning by using intentionally aberrated optical hardware. We demonstrate the use of an astigmatic spectral domain (SD-)OCM imaging system to enable single-acquisition volumetric OCM in 3D cell culture over an extended depth range, compared to a non-aberrated SD-OCM system. The transverse resolution of the non-aberrated and astigmatic imaging systems after application of CAO were 2 um and 2.2 um, respectively. The depth-range of effective signal collection about the nominal focal plane was increased from 100 um in the non-aberrated system to over 300 um in the astigmatic system, extending the range over which useful data may be acquired in a single OCM dataset. We anticipate that this method will enable high-throughput cellular-resolution imaging of dynamic biological systems over extended volumes.

  6. Sixth-order wave aberration theory of ultrawide-angle optical systems.

    Science.gov (United States)

    Lu, Lijun; Cao, Yiqing

    2017-10-20

    In this paper, we develop sixth-order wave aberration theory of ultrawide-angle optical systems like fisheye lenses. Based on the concept and approach to develop wave aberration theory of plane-symmetric optical systems, we first derive the sixth-order intrinsic wave aberrations and the fifth-order ray aberrations; second, we present a method to calculate the pupil aberration of such kind of optical systems to develop the extrinsic aberrations; third, the relation of aperture-ray coordinates between adjacent optical surfaces is fitted with the second-order polynomial to improve the calculation accuracy of the wave aberrations of a fisheye lens with a large acceptance aperture. Finally, the resultant aberration expressions are applied to calculate the aberrations of two design examples of fisheye lenses; the calculation results are compared with the ray-tracing ones with Zemax software to validate the aberration expressions.

  7. Foci of decreased signal on T2-weighted MR images in leiomyosarcomas of soft tissue: correlation between MR and histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Pilavaki, M. E-mail: mayiapil@otenet.gr; Drevelegas, A.; Nenopoulou, H.; Scordalaki, A.; Chourmouzi, D.; Sofroniadis, I.; Dimitriadis, A.S

    2004-09-01

    Objective: Leiomyosarcomas are rare soft tissue sarcomas with varying MR signal characteristics and histologic pictures. The purpose of this study was to investigate the histological features of foci, which showed decreased signal on T2-weighted images in leiomyosarcomas of soft tissue. Material and methods: We reviewed the MR images of six histologically proved cases of leiomyosarcomas of soft tissue and correlated the foci, which showed decreased signal on T2-weighted images with the histologic findings. Result: Microscopic examination revealed that these foci were composed of hyalinization of neoplastic tissue, internal septations, deposition of hemosiderin, or corresponded to metaplastic bone. Conclusion: The authors explain that the foci of decreased signal on T2-weighted MR images correspond to tissue components of the lesion, particularly fibrous tissue, hemosiderin and metaplastic bone. So, the suggestion is that leiomyosarcoma should be considered in the differential diagnosis of soft-tissue tumors that show foci of decreased signal on T2-weighted MR images.

  8. Vascular Ehlers–Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci

    Science.gov (United States)

    Park, Min A.; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

    2017-01-01

    Abstract Rationale: Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. Patient concerns: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Diagnoses: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. Interventions: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Outcomes: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. Lessons: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the

  9. Revisiting Cross-Channel Information Transfer for Chromatic Aberration Correction

    KAUST Repository

    Sun, Tiancheng

    2017-12-25

    Image aberrations can cause severe degradation in image quality for consumer-level cameras, especially under the current tendency to reduce the complexity of lens designs in order to shrink the overall size of modules. In simplified optical designs, chromatic aberration can be one of the most significant causes for degraded image quality, and it can be quite difficult to remove in post-processing, since it results in strong blurs in at least some of the color channels. In this work, we revisit the pixel-wise similarity between different color channels of the image and accordingly propose a novel algorithm for correcting chromatic aberration based on this cross-channel correlation. In contrast to recent weak prior-based models, ours uses strong pixel-wise fitting and transfer, which lead to significant quality improvements for large chromatic aberrations. Experimental results on both synthetic and real world images captured by different optical systems demonstrate that the chromatic aberration can be significantly reduced using our approach.

  10. Temporal dynamics of ocular aberrations: monocular vs binocular vision.

    Science.gov (United States)

    Mira-Agudelo, A; Lundström, L; Artal, P

    2009-05-01

    The temporal dynamics of ocular aberrations are important for the evaluation of, e.g. the accuracy of aberration estimates, the correlation to visual performance, and the requirements for real-time correction with adaptive optics. Traditionally, studies on the eye's dynamic behavior have been performed monocularly, which might have affected the results. In this study we measured aberrations and their temporal dynamics both monocularly and binocularly in the relaxed and accommodated state for six healthy subjects. Temporal frequencies up to 100 Hz were measured with a fast-acquisition Hartmann-Shack wavefront sensor having an open field-of-view configuration which allowed fixation to real targets. Wavefront aberrations were collected in temporal series of 5 s duration during binocular and monocular vision with fixation targets at 5 m and 25 cm distance. As expected, a larger temporal variability was found in the root-mean-square wavefront error when the eye accommodated, mainly for frequencies lower than 30 Hz. A statistically-significant difference in temporal behavior between monocular and binocular viewing conditions was found. However, on average it was too small to be of practical importance, although some subjects showed a notably higher variability for the monocular case during near vision. We did find differences in pupil size with mono- and binocular vision but the pupil size temporal dynamics did not behave in the same way as the aberrations' dynamics.

  11. Optical aberrations induced by subclinical decentrations of the ablation pattern

    Science.gov (United States)

    Mrochen, Michael; Kaemmerer, Maik; Riedel, Peter; Mierdel, Peter; Krinke, Hans-Eberhard; Seiler, Theo

    2000-06-01

    Purpose: The aim of this work was to study the effect of currently used ablation profiles along with eccentric ablations on the increase of higher order aberrations observed after PRK. Material and Methods: The optical aberrations of 10 eyes were tested before and after PRK. Refractive surgery was performed using a ArF-excimer laser system. In all cases, the ablation zone was 6 mm or larger. The spherical equivalent of the correction was ranging from -2.5 D to -6.0 D. The measured wavefront error was compared to numerical simulations done with the reduced eye model and currently used ablation profiles as well as compared with experimental results obtained from ablation on PMMA balls. Results: The aberration measurements result in a considerable change of the spherical- and coma-like wavefront errors. This result was in good correlation with the numerical simulations and the experimental results. Furthermore, it has been derived that the major contribution on the induced higher order aberrations are a result of the small decentration (less than 1.0 mm) of the ablation zone. Conclusions: Higher order spherical- and coma-like aberrations after PRK are mainly determined by the decentration of the ablation zone during laser refractive surgery. However, future laser systems should use efficient eye-tracking systems and aspherical ablation profiles to overcome this problem.

  12. Semen quality in men with Y chromosome aberrations.

    Science.gov (United States)

    Antonelli, A; Marcucci, L; Elli, R; Tanzi, N; Paoli, D; Radicioni, A; Lombardo, F; Lenzi, A; Gandini, L

    2011-10-01

    Infertile males sometimes bear structurally balanced chromosome aberrations, such as translocations and inversions, which involve both autosomes and sex chromosomes. The aim of this study was to evaluate genotype-phenotype correlations in a sample of infertile men with various types of Y chromosome abnormalities. In particular, we examined the effect of (i) balanced structural aberrations such as translocations between sex chromosomes and autosomes; (ii) unbalanced structural aberrations such as deletions or isodicentrics, both [idic(Yp)] and [idic(Yq)]. We studied 13 subjects bearing Y chromosome aberrations. Each patient underwent seminal fluid examination, andrological inspection, hormone study, testicular ultrasound, conventional and molecular cytogenetic analysis and study of Y chromosome microdeletions. Comparison of genotype and sperm phenotype in infertile patients with various Y chromosome aberrations revealed the key role of meiotic pairing defects in arresting spermatogenesis, both in the presence and in the absence of azoospermic factor microdeletions and cell mosaicism. The failure of meiosis and, in consequence, spermatogenesis may be a result of the failure to inactivate the X chromosome in the meiotic prophase, which is necessary for normal male spermatogenesis to take place. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  13. Anisotropic Complementary Acoustic Metamaterial for Canceling out Aberrating Layers

    Directory of Open Access Journals (Sweden)

    Chen Shen

    2014-11-01

    Full Text Available In this paper, we investigate a type of anisotropic, acoustic complementary metamaterial (CMM and its application in restoring acoustic fields distorted by aberrating layers. The proposed quasi two-dimensional (2D, nonresonant CMM consists of unit cells formed by membranes and side branches with open ends. Simultaneously, anisotropic and negative density is achieved by assigning membranes facing each direction (x and y directions different thicknesses, while the compressibility is tuned by the side branches. Numerical examples demonstrate that the CMM, when placed adjacent to a strongly aberrating layer, could acoustically cancel out that aberrating layer. This leads to dramatically reduced acoustic field distortion and enhanced sound transmission, therefore virtually removing the layer in a noninvasive manner. In the example where a focused beam is studied, using the CMM, the acoustic intensity at the focus is increased from 28% to 88% of the intensity in the control case (in the absence of the aberrating layer and the CMM. The proposed acoustic CMM has a wide realm of potential applications, such as cloaking, all-angle antireflection layers, ultrasound imaging, detection, and treatment through aberrating layers.

  14. Sub-ångstrom resolution using aberration corrected electron optics.

    Science.gov (United States)

    Batson, P E; Dellby, N; Krivanek, O L

    2002-08-08

    Following the invention of electron optics during the 1930s, lens aberrations have limited the achievable spatial resolution to about 50 times the wavelength of the imaging electrons. This situation is similar to that faced by Leeuwenhoek in the seventeenth century, whose work to improve the quality of glass lenses led directly to his discovery of the ubiquitous "animalcules" in canal water, the first hints of the cellular basis of life. The electron optical aberration problem was well understood from the start, but more than 60 years elapsed before a practical correction scheme for electron microscopy was demonstrated, and even then the remaining chromatic aberrations still limited the resolution. We report here the implementation of a computer-controlled aberration correction system in a scanning transmission electron microscope, which is less sensitive to chromatic aberration. Using this approach, we achieve an electron probe smaller than 1 A. This performance, about 20 times the electron wavelength at 120 keV energy, allows dynamic imaging of single atoms, clusters of a few atoms, and single atomic layer 'rafts' of atoms coexisting with Au islands on a carbon substrate. This technique should also allow atomic column imaging of semiconductors, for detection of single dopant atoms, using an electron beam with energy below the damage threshold for silicon.

  15. Primary chromatic aberration elimination via optimization work with genetic algorithm

    Science.gov (United States)

    Wu, Bo-Wen; Liu, Tung-Kuan; Fang, Yi-Chin; Chou, Jyh-Horng; Tsai, Hsien-Lin; Chang, En-Hao

    2008-09-01

    Chromatic Aberration plays a part in modern optical systems, especially in digitalized and smart optical systems. Much effort has been devoted to eliminating specific chromatic aberration in order to match the demand for advanced digitalized optical products. Basically, the elimination of axial chromatic and lateral color aberration of an optical lens and system depends on the selection of optical glass. According to reports from glass companies all over the world, the number of various newly developed optical glasses in the market exceeds three hundred. However, due to the complexity of a practical optical system, optical designers have so far had difficulty in finding the right solution to eliminate small axial and lateral chromatic aberration except by the Damped Least Squares (DLS) method, which is limited in so far as the DLS method has not yet managed to find a better optical system configuration. In the present research, genetic algorithms are used to replace traditional DLS so as to eliminate axial and lateral chromatic, by combining the theories of geometric optics in Tessar type lenses and a technique involving Binary/Real Encoding, Multiple Dynamic Crossover and Random Gene Mutation to find a much better configuration for optical glasses. By implementing the algorithms outlined in this paper, satisfactory results can be achieved in eliminating axial and lateral color aberration.

  16. Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

    Science.gov (United States)

    Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

    2013-01-01

    Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

  17. Visualisation of γH2AX foci caused by heavy ion particle traversal; distinction between core track versus non-track damage.

    Directory of Open Access Journals (Sweden)

    Nakako Izumi Nakajima

    Full Text Available Heavy particle irradiation produces complex DNA double strand breaks (DSBs which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle.

  18. MirrorCrypt

    OpenAIRE

    García Martínez, José María

    2014-01-01

    Este proyecto muestra la creación de una aplicación que permite trabajar con sistemas de almacenamiento en la nube de manera encriptada. Aquest projecte mostra la creació d'una aplicació que permet treballar amb sistemes d'emmagatzematge en el núvol de manera encriptada. Bachelor thesis for the Computer Science program on Computer security.

  19. Aberrations in preliminary design of ITER divertor impurity influx monitor

    Energy Technology Data Exchange (ETDEWEB)

    Kitazawa, Sin-iti, E-mail: kitazawa.siniti@jaea.go.jp [Naka Fusion Institute, Japan Atomic Energy Agency, JAEA, Naka 311-0193 (Japan); Ogawa, Hiroaki [Naka Fusion Institute, Japan Atomic Energy Agency, JAEA, Naka 311-0193 (Japan); Katsunuma, Atsushi; Kitazawa, Daisuke [Core Technology Center, Nikon Corporation, Yokohama 244-8533 (Japan); Ohmori, Keisuke [Customized Products Business Unit, Nikon Corporation, Mito 310-0843 (Japan)

    2015-12-15

    Highlights: • Divertor impurity influx monitor for ITER (DIM) is procured by JADA. • DIM is designed to observe light from nuclear fusion plasma directly. • DIM is under preliminary design phase. • The spot diagrams were suppressed within the core of receiving fiber. • The aberration of DIM is suppressed in the preliminary design. - Abstract: Divertor impurity influx monitor for ITER (DIM) is a diagnostic system that observes light from nuclear fusion plasma directly. This system is affected by various aberrations because it observes light from the fan-array chord near the divertor in the ultraviolet–near infrared wavelength range. The aberrations should be suppressed to the extent possible to observe the light with very high spatial resolution. In the preliminary design of DIM, spot diagrams were suppressed within the core of the receiving fiber's cross section, and the resulting spatial resolutions satisfied the design requirements.

  20. Prospects for electron beam aberration correction using sculpted phase masks.

    Science.gov (United States)

    Shiloh, Roy; Remez, Roei; Arie, Ady

    2016-04-01

    Technological advances in fabrication methods allowed the microscopy community to take incremental steps towards perfecting the electron microscope, and magnetic lens design in particular. Still, state of the art aberration-corrected microscopes are yet 20-30 times shy of the theoretical electron diffraction limit. Moreover, these microscopes consume significant physical space and are very expensive. Here, we show how a thin, sculpted membrane is used as a phase-mask to induce specific aberrations into an electron beam probe in a standard high resolution TEM. In particular, we experimentally demonstrate beam splitting, two-fold astigmatism, three-fold astigmatism, and spherical aberration. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Conformal dome aberration correction by designing the inner surface

    Science.gov (United States)

    Zhang, Wang; Chen, Shouqian; Fan, Zhigang

    2016-12-01

    The ray transmission models of optical domes were established, and the characteristics of the rays while passing through a hemispherical dome and a conformal dome were comparatively analysed. Acquiring the minimum deviated angles from the inner surface of the conformal dome was then determined to be the designing goal for reducing the dynamic aberrations. Based on this, the inner surface of the conformal dome was optimized and thus, the dynamic aberrations were reduced. Finally, a completely cooled conformal optical system was designed. The results show that the optical system have produced good imaging quality within all the fields of regard, which further illustrates that designing the inner surface of a conformal dome is an effective method for aberration correction.

  2. Correcting the Chromatic Aberration in Barrel Distortion of Endoscopic Images

    Directory of Open Access Journals (Sweden)

    Y. M. Harry Ng

    2003-04-01

    Full Text Available Modern endoscopes offer physicians a wide-angle field of view (FOV for minimally invasive therapies. However, the high level of barrel distortion may prevent accurate perception of image. Fortunately, this kind of distortion may be corrected by digital image processing. In this paper we investigate the chromatic aberrations in the barrel distortion of endoscopic images. In the past, chromatic aberration in endoscopes is corrected by achromatic lenses or active lens control. In contrast, we take a computational approach by modifying the concept of image warping and the existing barrel distortion correction algorithm to tackle the chromatic aberration problem. In addition, an error function for the determination of the level of centroid coincidence is proposed. Simulation and experimental results confirm the effectiveness of our method.

  3. An electron microscope for the aberration-corrected era.

    Science.gov (United States)

    Krivanek, O L; Corbin, G J; Dellby, N; Elston, B F; Keyse, R J; Murfitt, M F; Own, C S; Szilagyi, Z S; Woodruff, J W

    2008-02-01

    Improved resolution made possible by aberration correction has greatly increased the demands on the performance of all parts of high-end electron microscopes. In order to meet these demands, we have designed and built an entirely new scanning transmission electron microscope (STEM). The microscope includes a flexible illumination system that allows the properties of its probe to be changed on-the-fly, a third-generation aberration corrector which corrects all geometric aberrations up to fifth order, an ultra-responsive yet stable five-axis sample stage, and a flexible configuration of optimized detectors. The microscope features many innovations, such as a modular column assembled from building blocks that can be stacked in almost any order, in situ storage and cleaning facilities for up to five samples, computer-controlled loading of samples into the column, and self-diagnosing electronics. The microscope construction is described, and examples of its capabilities are shown.

  4. An electron microscope for the aberration-corrected era

    Energy Technology Data Exchange (ETDEWEB)

    Krivanek, O.L. [Nion Co., 1102 8th Street, Kirkland, WA 98033 (United States)], E-mail: krivanek.ondrej@gmail.com; Corbin, G.J.; Dellby, N.; Elston, B.F.; Keyse, R.J.; Murfitt, M.F.; Own, C.S.; Szilagyi, Z.S.; Woodruff, J.W. [Nion Co., 1102 8th Street, Kirkland, WA 98033 (United States)

    2008-02-15

    Improved resolution made possible by aberration correction has greatly increased the demands on the performance of all parts of high-end electron microscopes. In order to meet these demands, we have designed and built an entirely new scanning transmission electron microscope (STEM). The microscope includes a flexible illumination system that allows the properties of its probe to be changed on-the-fly, a third-generation aberration corrector which corrects all geometric aberrations up to fifth order, an ultra-responsive yet stable five-axis sample stage, and a flexible configuration of optimized detectors. The microscope features many innovations, such as a modular column assembled from building blocks that can be stacked in almost any order, in situ storage and cleaning facilities for up to five samples, computer-controlled loading of samples into the column, and self-diagnosing electronics. The microscope construction is described, and examples of its capabilities are shown.

  5. Split-plot fractional designs: Is minimum aberration enough?

    DEFF Research Database (Denmark)

    Kulahci, Murat; Ramirez, Jose; Tobias, Randy

    2006-01-01

    Split-plot experiments are commonly used in industry for product and process improvement. Recent articles on designing split-plot experiments concentrate on minimum aberration as the design criterion. Minimum aberration has been criticized as a design criterion for completely randomized fractional...... factorial design and alternative criteria, such as the maximum number of clear two-factor interactions, are suggested (Wu and Hamada (2000)). The need for alternatives to minimum aberration is even more acute for split-plot designs. In a standard split-plot design, there are several types of two...... for completely randomized designs. Consequently, we provide a modified version of the maximum number of clear two-factor interactions design criterion to be used for split-plot designs....

  6. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

    Science.gov (United States)

    Koshel, E. I.; Aleshin, V. V.; Eroshenko, G. A.; Kutyrev, V. V.

    2014-01-01

    Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina. PMID:24804197

  7. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

    Directory of Open Access Journals (Sweden)

    E. I. Koshel

    2014-01-01

    Full Text Available Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major, the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus, constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida. We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina.

  8. Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci

    Directory of Open Access Journals (Sweden)

    Solano Philippe

    2011-07-01

    Full Text Available Abstract Background Glossina palpalis palpalis (Diptera: Glossinidae is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo using eight microsatellite DNA markers. Results A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters. Conclusions This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.

  9. MR-guided stereotactic laser ablation of epileptogenic foci in children.

    Science.gov (United States)

    Curry, Daniel J; Gowda, Ashok; McNichols, Roger J; Wilfong, Angus A

    2012-08-01

    For about 30% of epilepsy patients, pharmaceutical therapy fails to control their seizures. MR-guided laser interstitial thermal therapy (MRgLITT) allows for real-time thermal monitoring of the ablation process and feedback control over the laser energy delivery. We report on minimally invasive surgical techniques of MRgLITT and short-term follow-up results from the first five pediatric cases in which this system was used to ablate focal epileptic lesions. We studied the patients with MRI of the brain, localized the seizure with video-EEG and used the Visualase Thermal Therapy 25 System for laser ablation of their seizure foci. All 5 patients are seizure free and there were no complications as of 2-13-month follow-up. MR-guided laser interstitial thermal therapy has a significant potential to be a minimally invasive alternative to more conventional techniques to surgically treat medically refractory epilepsy in children. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Three-dimensional quantitative ultrasound to guide pathologists towards metastatic foci in lymph nodes.

    Science.gov (United States)

    Mamou, Jonathan; Saegusa-Beecroft, Emi; Coron, Alain; Oelze, Michael L; Yamaguchi, Tadashi; Machi, Junji; Hata, Masaki; Yanagihara, Eugene; Laugier, Pascal; Feleppa, Ernest J

    2012-01-01

    The detection of metastases in freshly-excised lymph nodes from cancer patients during lymphadenectomy is critically important for cancer staging, treatment, and optimal patient management. Currently, conventional histologic methods suffer a high rate of false-negative determinations because pathologists cannot evaluate each excised lymph nodes in its entirety. Therefore, lymph nodes are undersampled and and small but clinically relevant metastatic regions can be missed. In this study, quantitative ultrasound (QUS) methods using high-frequency transducers (i.e., > 20 MHz) were developed and evaluated for their ability to detect and guide pathologists towards suspicious regions in lymph nodes. A custom laboratory scanning system was used to acquire radio-frequency (RF) data in 3D from excised lymph nodes using a 26-MHz center-frequency transducer. Overlapping 1-mm cylindrical regions-of-interest (ROIs) of the RF data were processed to yield 13 QUS estimates quantifying tissue microstructure and organization. These QUS methods were applied to more than 260 nodes from more than 160 colorectal-, gastric-, and breast-cancer patients. Cancer-detection performance was assessed for individual estimates and linear combinations of estimates. ROC results demonstrated excellent classification. For colorectal- and gastric-cancer nodes, the areas under the ROC curves (AUCs) were greater than 0.95. Slightly poorer results (AUC=0.85) were obtained for breast-cancer nodes. Images based on QUS parameters also permitted localization of cancer foci in some micrometastatic cases.

  11. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

  12. A review of Web information seeking research: considerations of method and foci of interest

    Directory of Open Access Journals (Sweden)

    Konstantina Martzoukou

    2005-01-01

    Full Text Available Introduction. This review shows that Web information seeking research suffers from inconsistencies in method and a lack of homogeneity in research foci. Background. Qualitative and quantitative methods are needed to produce a comprehensive view of information seeking. Studies also recommend observation as one of the most fundamental ways of gaining direct knowledge of behaviour. User-centred research emphasises the importance of holistic approaches, which incorporate physical, cognitive, and affective elements. Problems. Comprehensive studies are limited; many approaches are problematic and a consistent methodological framework has not been developed. Research has often failed to ensure appropriate samples that ensure both quantitative validity and qualitative consistency. Typically, observation has been based on simulated rather than real information needs and most studies show little attempt to examine holistically different characteristics of users in the same research schema. Research also deals with various aspects of cognitive style and ability with variant definitions of expertise and different layers of user experience. Finally the effect of social and cultural elements has not been extensively investigated. Conclusion. The existing limitations in method and the plethora of different approaches allow little progress and fewer comparisons across studies. There is urgent need for establishing a theoretical framework on which future studies can be based so that information seeking behaviour can be more holistically understood, and results can be generalised.

  13. Automatic detection of Hyperreflective Foci in optical coherence tomography B-scans using Morphological Component Analysis.

    Science.gov (United States)

    Mokhtari, Marzieh; Ghasemi Kamasi, Zeinab; Rabbani, Hossein

    2017-07-01

    Hyperreflective Foci (HF) is one of the most common complications distributed in cross-sectional images of patients with Diabetic Macular Edema (DME). Scanning Laser Ophthalmoscope (SLO) images usually consists of several B-scans that represent a cross-sectional reconstruction of a plane through the anterior or posterior regions of retina. In each B-scan, HFs are geometrically distinct constituents in different retinal layers. Since the intensity levels of HFs and many other subjects in B-scans are the same, in this paper we try to separate HFs from other objects by detection of the point and curve singularities in each B-scan. The decomposition algorithm presented in this paper is based on sparse image representation of B-scans using Morphological Component Analysis (MCA) technique. By using curvelet transform and Daubechies wavelet basis, two different over-complete dictionaries are constructed which represent two various aspects of B-scans. The HFs are more distinguished in reconstructed image with wavelet dictionary and other objects are mostly detectable by curvelet dictionary. So, HFs can be detected by applying an optimum threshold criterion on reconstructed image by wavelet atoms. Finally, the false positive points are reduced by removing the candidate points in RNFL and RPE layers, which are automatically segmented based on ridgelet transform. Our simulation results on 1924 HFs show that sensitivity and specificity for HF detection is 91.0% and 100%, respectively.

  14. Laser photocoagulation around extra foveolar foci of toxoplasma retinochoroiditis: a way to decrease frequency of recurrence

    Science.gov (United States)

    Labalette, P.; Desmettre, Thomas; Mordon, Serge R.; Constantinides, G.

    1995-01-01

    Thirty four patients with retinochoroiditis initially treated with medical treatment and later treated with laser photocoagulation around the foci were retrospectively evaluated for the risk of recurrence of the eretinochoroiditis. We used a Kaplan-Meier representation to show the evolution of the number of patients without recurrence as a function of time and as the number of patients followed up decreases (rate of patients without recurrence at 1 year: 86 +/- 12.3% for 26 patients exposed; at 2 years: 75 +/- 16.4% for 20 patients exposed; at 3 years and at 4 years 70 +/- 17% for 17 patients exposed). The recurrence rates were compared to the data previously published in the literature. We failed to demonstrate the efficacy of laser photocoagulation on inactive retinochoroiditis for prevention of recurrence of ocular toxoplasmosis. However, the heterogeneity of our series, the great amount of patients lost to follow up, and the heterogeneity of the recurrence rates of the literature contribute to explain that result.

  15. [Analysis of diversity and identification of the genovariants of plague agent strains from Mongolian foci].

    Science.gov (United States)

    Kukleva, L M; Shavina, N Yu; Odinokov, G N; Oglodin, E G; Nosov, N Yu; Vinogradova, N A; Guseva, N P; Eroshenko, G A; Kutyrev, V V

    2015-03-01

    The genetic diversity of Yersinia pestis strains from the Mongolian natural plague foci has been investigated. A total of 32 strains isolated from western, eastern, and central aimaks, as well as from the territory of the Gobi region, have been studied. Twenty-four strains belong to the main Y. pestis subspecies, while eight belong to other subspecies. There is only one strain of biovar medievalis (genovariant 2.MED1) among the strains of the main subspecies, while the rest of the subspecies belong to the biovar antiqua. Biovar antiqua strains are split into three groups. Strains from the eastern part of the country were classified as genovariant 2.ANT3, and those from the western and central regions were classified as genovariant 3.ANT2, which was endemic for Mongolia. One strain from the Bayan-Ulegeiskii aimak had the rare genovariant 4.ANT. None of the strains of the biovar antiqua belonged to its ancient 0.ANT branch, which is inconsistent with the commonly accepted idea that ancient marmot's plague agent race originates from Mongolia. Six out of eight strains of the minor subspecies belonged to the ulegeica subspecies, which are endemic to Mongolia, one strain belonged to the microtus group, and the last belonged to a previously uncharacterized variant of the minor subspecies.

  16. Motivational foci and asthma medication tactics directed towards a functional day

    Directory of Open Access Journals (Sweden)

    Lötvall Jan

    2011-10-01

    Full Text Available Abstract Background There appears to be an obvious gap between a medical and patient adherence perspective. Deviating from a medication prescription could be regarded as fairly irrational, but with respect to patients' goals and/or concerns it could be seen as understandable. Thus, the aim was to elucidate adherence reasoning in relation to asthma medication. Methods This was a qualitative study; data collection and analysis procedures were conducted according to Grounded Theory methodology. Eighteen persons, aged 22 with asthma and regular asthma medication treatment, were interviewed. Results The emerged theoretical model illustrated that adherence to asthma medication was motivated by three foci, all directed towards a desired outcome in terms of a functional day as desired by the patient. A promotive focus was associated with the ambition to achieve a positive asthma outcome by being adherent either to the received prescription or to a self-adjusted dosage. A preventive focus was intended to ensure avoidance of a negative asthma outcome either by sticking to the prescription or by preventively overusing the medication. A permissive focus was associated with unstructured adherence behaviour in which medication intake was primarily triggered by asthma symptoms. Conclusions As all participants had consciously adopted functioning medication tactics that directed them towards the desired goal of a functional day. In an effort to bridge the gap between a patient- and a medical adherence perspective, patients need support in defining their desired functionality and guidance in developing a person-based medication tactic.

  17. [Social bases for the functioning of nanophyetiasis foci in the Amur region].

    Science.gov (United States)

    Dragomeretskaia, A G; Zelia, O P; Trotsenko, O E; Ivanova, I B

    2014-01-01

    Parasitological examination of the population of the Amur Region has revealed that the nanophyetiasis foci affecting as high as 28.4% of the people are being preserved and functioning now; at the same time the highest rates of infection with the trematode Nanophyetus salmincola schikhobalowi are seen in the dwellers of the populated areas situated on the banks of the mountain Amur tributaries. It has been ascertained that the major season when the population is infected with Nanophyetus is summer and its highest incidence are noted in autumn (November) after the active fishing season is completed. It has been found that infection occurs in infants and the maximum incidence is in the age group of 21-30 years (45.5%) and remains virtually the same in a middle-aged population [31-50 years (37.0-42.2%)], by decreasing slightly in the older age groups (18.2-21.7%). According to the questionnaire survey data, fish (90% of its species are an intermediate host for Nanophyetus) is a staple food in the population of the highest incidence rural areas. The major causes of Nanophyetus infection are the wide consumption of raw and low-salt fish and a low population awareness of measures to prevent helminthiasis, the transmission factor of which is fish.

  18. The BHVI-EyeMapper: peripheral refraction and aberration profiles.

    Science.gov (United States)

    Fedtke, Cathleen; Ehrmann, Klaus; Falk, Darrin; Bakaraju, Ravi C; Holden, Brien A

    2014-10-01

    The aim of this article was to present the optical design of a new instrument (BHVI-EyeMapper, EM), which is dedicated to rapid peripheral wavefront measurements across the visual field for distance and near, and to compare the peripheral refraction and higher-order aberration profiles obtained in myopic eyes with and without accommodation. Central and peripheral refractive errors (M, J180, and J45) and higher-order aberrations (C[3, 1], C[3, 3], and C[4, 0]) were measured in 26 myopic participants (mean [±SD] age, 20.9 [±2.0] years; mean [±SD] spherical equivalent, -3.00 [±0.90] diopters [D]) corrected for distance. Measurements were performed along the horizontal visual field with (-2.00 to -5.00 D) and without (+1.00 D fogging) accommodation. Changes as a function of accommodation were compared using tilt and curvature coefficients of peripheral refraction and aberration profiles. As accommodation increased, the relative peripheral refraction profiles of M and J180 became significantly (p 0.05). The peripheral aberration profiles of C[3, 1], C[3, 3], and C[4, 0] became significantly (p refraction and higher-order aberration profiles occurred during accommodation in myopic eyes. With its extended measurement capabilities, that is, permitting rapid peripheral refraction and higher-order aberration measurements up to visual field angles of ±50 degrees for distance and near (up to -5.00 D), the EM is a new advanced instrument that may provide additional insights in the ongoing quest to understand and monitor myopia development.

  19. Reducing starbursts in highly aberrated eyes with pupil miosis.

    Science.gov (United States)

    Xu, Renfeng; Kollbaum, Pete; Thibos, Larry; Lopez-Gil, Norberto; Bradley, Arthur

    2018-01-01

    To test the hypothesis that marginal ray deviations determine perceived starburst sizes, and to explore different strategies for decreasing starburst size in highly aberrated eyes. Perceived size of starburst images and visual acuities were measured psychophysically for eyes with varying levels of spherical aberration, pupil sizes, and defocus. Computationally, we use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-LASIK eyes to quantify the image quality (the visually weighted Strehl ratio derived from the optical transfer function, VSOTF) with different pupil sizes at both photopic and mesopic light levels. For distance corrected post-LASIK and keratoconic eyes with a night-time pupil (e.g., 7 mm), the starburst diameter is about 1.5 degrees (1 degree for normal presbyopic eyes), which can be reduced to ≤0.25 degrees with pupil sizes ≤3 mm. Starburst size is predicted from the magnitude of the longitudinal spherical aberration. Refracting the eye to focus the pupil margin also removed starbursts, but, unlike small pupils, significantly degraded visual acuity. Reducing pupil diameter to 3 mm improved image quality for these highly aberrated eyes by about 2.7 ×  to 1.7 ×  relative to the natural pupils when light levels were varied from 0.1 to 1000 cd m-2 , respectively. Subjects with highly aberrated eyes observed larger starbursts around bright lights at night predictable by the deviated marginal rays. These were effectively attenuated by reducing pupil diameters to ≤3 mm, which did not cause a drop in visual acuity or modelled image quality even at mesopic light levels. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

  20. In vivo crypt surface hyperproliferation is decreased by butyrate and increased by deoxycholate in normal rat colon: associated in vivo effects on c-Fos and c-Jun expression.

    Science.gov (United States)

    Velázquez, O C; Zhou, D; Seto, R W; Jabbar, A; Choi, J; Lederer, H M; Rombeau, J L

    1996-01-01

    Studies on colon carcinogenesis suggest that the short-chain fatty acid butyrate may be protective, whereas the secondary bile acid deoxycholate may promote tumor development. Crypt surface hyperproliferation is regarded as a biomarker of colon cancer risk and can be modulated in vitro by the differentiation inducer butyrate and the tumor promoter deoxycholate. We hypothesized that butyrate decreases and deoxycholate increases crypt surface proliferation in vivo and that these effects are mediated by changes in the expression of the protooncogenes c-Fos and c-Jun, which are known to regulate proliferation and differentiation. Twenty-five adult Sprague-Dawley rats underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L sodium chloride, 10 mmol/ L sodium butyrate, or 10 mmol/L sodium deoxycholate. Proliferation of the whole crypt and five crypt compartments from base to surface was assessed by proliferating cell nuclear antigen immunohistochemistry. The øh value, an index of "premalignant" hyperproliferation, was calculated as the ratio of labeled cells in the two surface compartments divided by the labeled cells in the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot. Crypt surface proliferation and the øh value were significantly decreased by butyrate and increased by deoxycholate. Butyrate increased colonic expression of c-Jun, whereas deoxycholate significantly induced c-Fos. The in vivo effects on surface proliferation are consistent with a potential protective [corrected] role for butyrate and a promotive role for deoxycholate in colon carcinogenesis. The concurrently observed effects on colonic c-Jun and c-Fos expression represent a novel finding and suggest that direct or indirect modulation of protooncogene expression may be the mechanism by which these dietary byproducts regulate proliferation in vivo.

  1. Experimental demonstration of a light beam with superior aberration resilience.

    Science.gov (United States)

    Gaffar, Md; Kalita, Ranjan; Boruah, Bosanta R

    2016-10-01

    In this Letter, we present the experimental results of a focused light beam that exhibits superior resilience to various common monochromatic aberrations. The light beam, obtained by applying a helical phase mask on an azimuthally polarized beam, has an Airy pattern that is like a circularly symmetric focal spot. Our results show that the beam in the presence of aberrations has better performance in terms of the Strehl ratio and the effect on the radius of the encircled energy relative to a normal linearly polarized or circularly polarized beam. Our experimental results agree well with the corresponding theoretical results.

  2. [Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].

    Science.gov (United States)

    Gregor, V; Sípek, A; Sípek, A; Horácek, J '; Langhammer, P; Petrzílková, L; Calda, P

    2009-02-01

    An analysis of prenatal diagnostics efficiency of selected types of chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data according to particular selected diagnoses. Retrospective epidemiological analysis of pre- and postnatal chromosomal aberrations diagnostics and its efficiency. Data on pre- and postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were used. Data on prenatally diagnosed birth defects (and for terminated pregnancies) were collected from particular departments of prenatal diagnostics, medical genetics and ultrasound diagnostics in the Czech Republic, data on birth defects in births from the National Birth Defects Register (Institute for Health Information and Statistics). Total numbers over the period under the study, mean incidences of selected types of chromosomal aberrations and mean prenatal diagnostics efficiencies were analyzed. Following chromosomal aberrations were studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes 47,XXX and 47,XYY. A relative proportion of Down, Edwards and Patau syndromes as well as other autosomal and gonosomal aberration is presented in figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal aberrations in selectively aborted fetuses, in other pregnancies, "other chromosomal aberrations" category (mostly balanced reciprocal translocations and inversions) present more than 2/3 of all diagnoses. During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%. The study gives updated results of

  3. Aberration Theory - A Spectrum Of Design Techniques For The Perplexed

    Science.gov (United States)

    Shafer, David

    1986-10-01

    The early medieval scholar Maimonides wrote a famous book called "Guide for the Perplexed", which explained various thorny philosophical and religious questions for the benefit of the puzzled novice. I wish I had had such a person to guide me when I first started a career in lens design. There the novice is often struck by how much of an "art" this endeavor is. The best bet, for a beginner with no experience, should be to turn to optical aberration theory - which, in principle, should explain much of what goes into designing an optical system. Unfortunately, this subject is usually presented in the form of proofs and derivations, with little time spent on the practical implications of aberration theory. Furthermore, a new generation of lens designers, who grew up with the computer, often consider aberration theory as an unnecessary relic from the past. My career, by contrast, is based on the conviction that using the results of aberration theory is the only intelligent way to design optical systems. Computers are an invaluable aide, but we must, ultimately, bite the bullet and think. Along these lines, I have given several papers over the last few years which deal directly with the philosophy of lens design; the kind of guides for the perplexed that I wished I had had from the start. These papers include: "Lens design on a desert island - A simple method of optical design", "A modular method of optical design", "Optical design with air lenses", "Optical design with 'phantom' aspherics", "Optical design methods: your head as a personal computer", "Aberration theory and the meaning of life", and a paper at Innsbruck - "Some interesting correspondences in aberration theory". In all cases, the emphasis is on using your head to think, and the computer to help you out with the numerical work and the "fine-tuning" of a design. To hope that the computer will do the thinking for you is folly. Solutions gained by this route rarely equal the results of an experienced and

  4. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    Science.gov (United States)

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-07-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1-3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure.

  5. Aberration of a negative ion beam caused by space charge effect

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, K. [Naruto University of Education, 748 Nakashima, Takashima, Naruto-cho, Naruto-shi, Tokushima 772-8502 (Japan); Wada, S.; Hatayama, A. [Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan)

    2010-02-15

    Aberrations are inevitable when the charged particle beams are extracted, accelerated, transmitted, and focused with electrostatic and magnetic fields. In this study, we investigate the aberration of a negative ion accelerator for a neutral beam injector theoretically, especially the spherical aberration caused by the negative ion beam expansion due to the space charge effect. The negative ion current density profiles with the spherical aberration are compared with those without the spherical aberration. It is found that the negative ion current density profiles in a log scale are tailed due to the spherical aberration.

  6. Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: insights into the worldwide expansion of Central Asia plague foci.

    Directory of Open Access Journals (Sweden)

    Yanjun Li

    Full Text Available BACKGROUND: The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical non-human pathogenic biovar Microtus (alias Pestoides including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. METHODOLOGY/PRINCIPAL FINDINGS: Multi-locus VNTR analysis (MLVA with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU, Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. CONCLUSIONS/SIGNIFICANCE: The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA

  7. Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: insights into the worldwide expansion of Central Asia plague foci.

    Science.gov (United States)

    Li, Yanjun; Cui, Yujun; Hauck, Yolande; Platonov, Mikhail E; Dai, Erhei; Song, Yajun; Guo, Zhaobiao; Pourcel, Christine; Dentovskaya, Svetlana V; Anisimov, Andrey P; Yang, Ruifu; Vergnaud, Gilles

    2009-06-22

    The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical) non-human pathogenic biovar Microtus (alias Pestoides) including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. Multi-locus VNTR analysis (MLVA) with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU), Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA25 assay provide an unprecedented view on the expansion and microevolution of Y

  8. Photo catalogue for the classification of foci in the BALB/c 3T3 cell transformation assay.

    Science.gov (United States)

    Sasaki, Kiyoshi; Bohnenberger, Susanne; Hayashi, Kumiko; Kunkelmann, Thorsten; Muramatsu, Dai; Poth, Albrecht; Sakai, Ayako; Salovaara, Susan; Tanaka, Noriho; Thomas, B Claire; Umeda, Makoto

    2012-04-11

    This catalogue is a display of focus photos representative of the BALB/c 3T3 cell transformation assay (CTA). It is intended as a visual aid for the identification and the scoring of foci in the conduct of the assay. A proper training from experienced personnel together with the protocol reported in this issue and the present photo catalogue will support method transfer and consistency in the assay results. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. RNA/MBNL1-containing foci in myoblast nuclei from patients affected by myotonic dystrophy type 2: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    C. Pellicciari

    2009-09-01

    Full Text Available Myotonic dystrophy type 2 (DM2 is a dominantly inherited autosomal disease with multi-systemic clinical features and it is caused by expansion of a CCTG tetranucleotide repeat in the first intron of the zinc finger protein 9 (ZNF9 gene in 3q21.The expanded-CCUG-containing transcripts are retained in the cell nucleus and accumulate in the form of focal aggregates which specifically sequester the muscleblind-like 1 (MBNL1 protein, a RNA binding factor involved in the regulation of alternative splicing. The structural organization and composition of the foci are still incompletely known. In this study, the nuclear foci occurring in cultured myoblasts from DM2 patients were characterised at fluorescence and transmission electron microscopy by using a panel of antibodies recognizing transcription and processing factors of pre-mRNAs. MBNL1 proved to co-locate in the nuclear foci with snRNPs and hnRNPs, whereas no co-location was observed with RNA polymerase II, the non-RNP splicing factor SC35, the cleavage factor CStF and the PML protein. At electron microscopy the MBNL1-containing nuclear foci appeared as roundish domains showing a rather homogeneous structure and proved to contain snRNPs and hnRNPs. The sequestration of splicing factors involved in early phases of pre-mRNA processing supports the hypothesis of a general alteration in the maturation of several mRNAs, which could lead to the multiple pathological dysfunctions observed in dystrophic patients.

  10. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

    2006-02-22

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

  11. Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating mouse cerebellar neuronal progenitors and medulloblastoma.

    Science.gov (United States)

    Deng, Zhong; Wang, Zhuo; Xiang, Chaomei; Molczan, Aliah; Baubet, Valérie; Conejo-Garcia, Jose; Xu, Xiaowei; Lieberman, Paul M; Dahmane, Nadia

    2012-09-15

    Telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence. Most eukaryotic telomeres can be transcribed to generate a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous nuclear RNA and can be developmentally regulated. However, the precise function and regulation of TERRA in normal and cancer cell development remains poorly understood. Here, we show that TERRA accumulates in highly proliferating normal and cancer cells, and forms large nuclear foci, which are distinct from previously characterized markers of DNA damage or replication stress. Using a mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling, TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates could also be detected in highly proliferating zones of progenitor neurons. SHH could enhance TERRA expression in purified granule progenitor cells in vitro, suggesting that proliferation signals contribute to TERRA expression in responsive tissue. TERRA foci did not colocalize with γH2AX foci, promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue. We also provide evidence that TERRA is elevated in a variety of human cancers. These findings suggest that elevated TERRA levels reflect a novel early form of telomere regulation during replication stress and cancer cell evolution, and the TERRA RNA aggregates may form a novel nuclear body in highly proliferating mammalian cells.

  12. Thermal lensing measurement from the coefficient of defocus aberration

    CSIR Research Space (South Africa)

    Bell, Teboho

    2016-03-01

    Full Text Available We measured the thermally induced lens from the coefficient of defocus aberration using a Shack-Hartmann wavefront sensor (SHWFS). As a calibration technique, we infer the focal length of standard lenses probed by a collimated Gaussian beam...

  13. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    Expressions for third-order aberration theory for holographic images. S K Tripathy S Ananda Rao. Brief Reports Volume 60 Issue 1 January 2003 pp 151-157 ... Author Affiliations. S K Tripathy1 S Ananda Rao1. Department of Physics, Jagannath Institute for Technology and Management, Parlakhemundi 761 200, India ...

  14. Intrachanges as part of complex chromosome-type exchange aberrations

    NARCIS (Netherlands)

    Boei, JJWA; Vermeulen, S; Moser, J; Mullenders, LHF; Natarajan, AT

    2002-01-01

    The chromosome-type exchange aberrations induced by ionizing radiation during the G(0)/G(1) phase of the cell cycle are believed to be the result of illegitimate rejoining of chromosome breaks. From numerous studies using chromosome painting, it has emerged that even after a moderate dose of

  15. Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that ...

    African Journals Online (AJOL)

    Lusoria artery or aberrant right subclavian artery (ARSA) is a rare anatomical variation of the origin of the right subclavian artery. Essentially, right subclavian artery originates from the brachiocephalic artery, but in 0.4-1.8% of the general population it may arise directly from the aortic arch distal to the left subclavian artery.

  16. Aberrant behavior of preschool children: Evaluation of questionnaire

    Directory of Open Access Journals (Sweden)

    Fajgelj Stanislav

    2007-01-01

    Full Text Available In the study metric characteristics of children aberrant behavior questionnaire were analyzed. The analysis was performed on the sample of 1.165 children, aged 4-7, in preschool institutions in several towns of Vojvodina. The questionnaire contained 36 items of the Likert-type scale and was filled in by one parent of each child. The authors examined main metric characteristics of the complete questionnaire, as well as individual items under the Rasche’s measurement model. Generally, parents seldom notice aberrant behavior in their children. Most frequently they notice stubbornness, while very rarely torturing of animals. The item discrimination, on the whole, was found satisfying. The reliability of the questionnaire is 0.84., and all indicators of misfit are within satisfactory ranges. According to differential functioning of the items, the authors found gender and age specificities of parents’ evaluation of aberrant behavior of their children. Parents often notice stubbornness and moldiness in girls, and aggression in boys. According to the parent’s observations, younger children are characterized by nail nibbling, ticklishness, and fearfulness, whereas older children show a tendency to force their way by crying, waywardness and bed-wetting. By means of factor analysis of the items, three principal facets of aberrant behavior were determined: overindulgence, shyness and quarrelsomeness. Cross validation (hold out showed that these three facets were robust in relation to the selection of the sample.

  17. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer

    DEFF Research Database (Denmark)

    Bonassi, Stefano; Norppa, Hannu; Ceppi, Marcello

    2008-01-01

    Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single...

  18. Thermally induced lensing determination from the coefficient of defocus aberration

    CSIR Research Space (South Africa)

    Bell, Teboho

    2014-07-01

    Full Text Available The effects of a temperature gradient in a laser crystal in an end-pumped configuration in a solid-state laser resonator results in thermally induced aberrations. Of particular interest we measure the thermally induced lens from the coefficient...

  19. Axial chromatic aberration of the human eye: frequency or wavelength?

    Science.gov (United States)

    Pease, P L; Barbeito, R

    1989-04-01

    The axial chromatic aberration of the human eye is nearly perfectly described by a linear function when expressed in terms of frequency rather than wavelength. Since linear functions are simple to work with and more readily understood, there are advantages for the expression of these data in terms of frequency.

  20. Joint denoising, demosaicing, and chromatic aberration correction for UHD video

    Science.gov (United States)

    Jovanov, Ljubomir; Philips, Wilfried; Damstra, Klaas Jan; Ellenbroek, Frank

    2017-09-01

    High-resolution video capture is crucial for numerous applications such as surveillance, security, industrial inspection, medical imaging and digital entertainment. In the last two decades, we are witnessing a dramatic increase of the spatial resolution and the maximal frame rate of video capturing devices. In order to achieve further resolution increase, numerous challenges will be facing us. Due to the reduced size of the pixel, the amount of light also reduces, leading to the increased noise level. Moreover, the reduced pixel size makes the lens imprecisions more pronounced, which especially applies to chromatic aberrations. Even in the case when high quality lenses are used some chromatic aberration artefacts will remain. Next, noise level additionally increases due to the higher frame rates. To reduce the complexity and the price of the camera, one sensor captures all three colors, by relying on Color Filter Arrays. In order to obtain full resolution color image, missing color components have to be interpolated, i.e. demosaicked, which is more challenging than in the case of lower resolution, due to the increased noise and aberrations. In this paper, we propose a new method, which jointly performs chromatic aberration correction, denoising and demosaicking. By jointly performing the reduction of all artefacts, we are reducing the overall complexity of the system and the introduction of new artefacts. In order to reduce possible flicker we also perform temporal video enhancement. We evaluate the proposed method on a number of publicly available UHD sequences and on sequences recorded in our studio.

  1. Measurement of low-order aberrations with an autostigmatic microscope

    Science.gov (United States)

    Kuhn, William P.

    2017-08-01

    The addition of a piezo-electric focusing stage and phase retrieval algorithms to a compact, adaptable autostigmatic microscope provides for both improved focus sensitivity during optical system alignment as well as the ability to measure low-order aberrations for system qualification. A description of the instrument and initial results are reported.

  2. Municipal landfill leachates induced chromosome aberrations in rat ...

    African Journals Online (AJOL)

    This study examined the potential mutagenic effects of raw and simulated leachates from Olushosun municipal solid waste (MSW) landfill using rat bone marrow chromosome aberration assay. Raw leachate obtained directly from the landfill and simulated leachate obtained via the American Society for Testing and Materials ...

  3. Municipal landfill leachates induced chromosome aberrations in rat ...

    African Journals Online (AJOL)

    user

    2006-11-16

    Nov 16, 2006 ... leachate induced chromosome aberration in rat. Other reports on leachate induced genotoxicity in Allium cepa. (Cabrera and Rodriguez, 1999; Bakare and Wale-. Adeyemo, 2004; Chandra et al., 2005.), Vicia faba. (Radetski et al., 2004; Sang and Li, 2004), Drosophila melanogaster (Siddique et al., 2005) ...

  4. Aberrant Pattern of Scanning in Prosopagnosia Reflects Impaired Face Processing

    Science.gov (United States)

    Stephan, Blossom Christa Maree; Caine, Diana

    2009-01-01

    Visual scanpath recording was used to investigate the information processing strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to controls, SC showed an aberrant pattern of scanning, directing attention away from the internal configuration of facial features (eyes, nose) towards peripheral regions (hair, forehead) of the…

  5. Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia.

    Directory of Open Access Journals (Sweden)

    Ebako N Takem

    Full Text Available In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community.The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses.A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7 [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124 [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001, while the seroprevalence was 7.8% (234/2994 [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997 [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973 [95% CI = 16.5-23.2 for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920.This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.

  6. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  7. The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies

    Directory of Open Access Journals (Sweden)

    Arturo Sousa

    2014-08-01

    Full Text Available The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS, using the Inverse Distance Weighted (IDW interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura, the presence of another vector (Anopheles labranchiae besides A. atroparvus (Levante or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia. In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  8. First Detection of Leishmania major DNA in Sergentomyia (Spelaeomyia) darlingi from Cutaneous Leishmaniasis Foci in Mali

    Science.gov (United States)

    Berdjane-Brouk, Zohra; Koné, Abdoulaye K.; Djimdé, Abdoulaye A.; Charrel, Rémi N.; Ravel, Christophe; Delaunay, Pascal; del Giudice, Pascal; Diarra, Adama Z.; Doumbo, Siala; Goita, Siaka; Thera, Mahamadou A.; Depaquit, Jérôme; Marty, Pierre; Doumbo, Ogobara K.; Izri, Arezki

    2012-01-01

    Background Leishmania major complex is the main causative agent of zoonotic cutaneous leishmaniasis (ZCL) in the Old World. Phlebotomus papatasi and Phlebotomus duboscqi are recognized vectors of L. major complex in Northern and Southern Sahara, respectively. In Mali, ZCL due to L. major is an emerging public health problem, with several cases reported from different parts of the country. The main objective of the present study was to identify the vectors of Leishmania major in the Bandiagara area, in Mali. Methodology/Principal Findings An entomological survey was carried out in the ZCL foci of Bandiagara area. Sandflies were collected using CDC miniature light traps and sticky papers. In the field, live female Phlebotomine sandflies were identified and examined for the presence of promastigotes. The remaining sandflies were identified morphologically and tested for Leishmania by PCR in the ITS2 gene. The source of blood meal of the engorged females was determined using the cyt-b sequence. Out of the 3,259 collected sandflies, 1,324 were identified morphologically, and consisted of 20 species, of which four belonged to the genus Phlebotomus and 16 to the genus Sergentomyia. Leishmania major DNA was detected by PCR in 7 of the 446 females (1.6%), specifically 2 out of 115 Phlebotomus duboscqi specimens, and 5 from 198 Sergentomyia darlingi specimens. Human DNA was detected in one blood-fed female S. darlingi positive for L. major DNA. Conclusion Our data suggest the possible involvement of P. duboscqi and potentially S. darlingi in the transmission of ZCL in Mali. PMID:22276095

  9. Automated detection of presence of mucus foci in airway diseases: preliminary results

    Science.gov (United States)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Ko, Jane; Godoy, Myrna C. B.

    2009-02-01

    Chronic Obstructive Pulmonary Disease (COPD) is often characterized by partial or complete obstruction of airflow in the lungs. This can be due to airway wall thickening and retained secretions, resulting in foci of mucoid impactions. Although radiologists have proposed scoring systems to assess extent and severity of airway diseases from CT images, these scores are seldom used clinically due to impracticality. The high level of subjectivity from visual inspection and the sheer number of airways in the lungs mean that automation is critical in order to realize accurate scoring. In this work we assess the feasibility of including an automated mucus detection method in a clinical scoring system. Twenty high-resolution datasets of patients with mild to severe bronchiectasis were randomly selected, and used to test the ability of the computer to detect the presence or absence of mucus in each lobe (100 lobes in all). Two experienced radiologists independently scored the presence or absence of mucus in each lobe based on the visual assessment method recommended by Sheehan et al [1]. These results were compared with an automated method developed for mucus plug detection [2]. Results showed agreement between the two readers on 44% of the lobes for presence of mucus, 39% of lobes for absence of mucus, and discordant opinions on 17 lobes. For 61 lobes where 1 or both readers detected mucus, the computer sensitivity was 75.4%, the specificity was 69.2%, and the positive predictive value (PPV) was 79.3%. Six computer false positives were a-posteriori reviewed by the experts and reassessed as true positives, yielding results of 77.6% sensitivity, 81.8% for specificity, and 89.6% PPV.

  10. Experiences with the control of schistosomiasis mansoni in two foci in Central Africa

    Directory of Open Access Journals (Sweden)

    B. Gryseels

    1992-01-01

    Full Text Available Experiences with population-based chemotherapy and other methods for the control of schistosomiasis mansoni in two subsaharan foci are described. In the forest area of Maniema (Zaire, intense transmission of Schistosoma mansoni, high prevalences and intensities of infection, and important morbidity have been documental. Taking into account the limited financial means and the poor logistic conditions, the control strategy has been based mainly on targeted chemotherapy of heavily infected people (>600 epg. After ten years of intervention, prevalences and intensities have hardly been affected, but the initial severe hepatosplenic morbidity has almost disappeared. In Burundi, a national research and control programme has been initiated in 1982. Prevalences, intensities and morbidity were moderate, transmission was focal and erratic in time and space. A more structural control strategy was developed, based on screening and selective therapy, health education, sanitation and domestic water supply. Prevalences and intensities have been considerably reduced, though the results show focal and unpredicatable variations. Transmission and reinfection were not signifcantly affected by chemotherapy alone, and eventual outcome of repeated selective treatment appears to be limited by the sensitivity of the screening method. Intestinal morbidity was strongly reduced by community-based selective treatment, but hepatosplenic enlargement was hardly affected; this is possibly due to the confounding impact of increasing malaria morbidity. The experiences show the importance of local structures and conditions for the development of an adapted control strategy. It is further concluded that population-based chemotherapy is a highly valid tool for the rapid control of morbidity, but should in most operational conditions not be considered as a tool for transmission control. Integration of planning, execution and surveillance in regular health services...

  11. Natural foci of Borrelia lusitaniae in a mountain region of Central Europe.

    Science.gov (United States)

    Tarageľová, Veronika Rusňáková; Mahríková, Lenka; Selyemová, Diana; Václav, Radovan; Derdáková, Markéta

    2016-03-01

    Lyme borreliosis is the most prevalent tick-borne disease in Europe. It is caused by spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex and transmitted to humans by ticks of the genus Ixodes. Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana are the most common genospecies in Central Europe. In contrast, Borrelia lusitaniae predominates in Mediterranean countries such as Portugal, Morocco, and Tunisia. In Slovakia, its prevalence is low and restricted to only a few sites. The aim of our research was to study the expansion of ticks into higher altitudes in the ecosystem of the Malá Fatra mountains (north Slovakia) and their infection with B. burgdorferi s.l. pathogens. Questing ticks were collected by flagging in seven years (2004, 2006-2011) at three different altitudes: low (630-660 m above sea level (ASL)), intermediate (720-750 m ASL), and high (1040-1070 m ASL). Tick abundance was highest at the lowest altitude and lowest at the highest altitude. The average infection prevalence of B. burgdorferi s.l. in nymphs and adults was 16.8% and 36.2%, respectively. The number of infected ticks decreased from 38.5% at the lowest altitude to 4.4% at the highest altitude. B. lusitaniae was the most frequently found genospecies (>60% of the ticks found positive for B. burgdorferi s.l.) in all sites in all the studied years with the exception of 2008 when B. afzelii predominated (62%). Our study confirms the spread of Ixodes ricinus ticks to higher altitudes in Slovakia. The discovery that our mountain study sites were a natural foci of B. lusitaniae was unexpected because this genospecies is usually associated with lizards and xerothermic habitats. Copyright © 2015 Elsevier GmbH. All rights reserved.

  12. Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia.

    Science.gov (United States)

    Takem, Ebako N; Affara, Muna; Amambua-Ngwa, Alfred; Okebe, Joseph; Ceesay, Serign J; Jawara, Musa; Oriero, Eniyou; Nwakanma, Davis; Pinder, Margaret; Clifford, Caitlin; Taal, Makie; Sowe, Momodou; Suso, Penda; Mendy, Alphonse; Mbaye, Amicoleh; Drakeley, Chris; D'Alessandro, Umberto

    2013-01-01

    In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community. The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses. A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7) [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124) [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001), while the seroprevalence was 7.8% (234/2994) [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997) [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973) [95% CI = 16.5-23.2) for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920). This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.

  13. Factor Structure, Reliability, and Validity of the Spanish Version of the Children's Florida Obsessive Compulsive Inventory (C-FOCI).

    Science.gov (United States)

    Piqueras, José A; Rodríguez-Jiménez, Tíscar; Ortiz, Ana G; Moreno, Elena; Lázaro, Luisa; Storch, Eric A

    2017-02-01

    The Children's Florida Obsessive Compulsive Inventory (C-FOCI) is a promising self-report measure of the presence and severity of obsessive-compulsive symptoms in children and adolescents. Although initial research showed it to have adequate psychometric properties, only one study has been published to date, which dealt exclusively with children. The aim of this report was to examine the psychometric properties of the C-FOCI across clinical and community samples of children and adolescents. The sample consisted of 94 Spanish-speaking patients with obsessive-compulsive disorder (OCD) and 1068 healthy community controls, aged 8-19 years. Factor analysis supported two single and independent factors (severity and symptoms), as well as metric invariance across groups for the symptom checklist and the Severity Scale. Results also indicated good reliability in terms of internal consistency and temporal stability, significant and high correlations with other OCD measures, and acceptable sensitivity and specificity for detect OCD. In summary, the C-FOCI is a promising, brief measure of 22 items for screening OCD symptoms and severity in children and adolescents.

  14. Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

    DEFF Research Database (Denmark)

    Breinholt, Vibeke M.; Mølck, Anne-Marie; Svendsen, Gitte Winkel

    2003-01-01

    mechanisms were assayed in blood, liver and colon and the impact of the antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (200 mg/kg diet) served as a pro-oxidant, genotoxicity and general...... toxicity control. IQ increased the levels of protein and DNA oxidation products in plasma, the area of glutathione S-transferase-placental form positive (GST-P) foci in the liver as well as the number of colonic aberrant crypt foci (ACF). All antioxidants and the antioxidant combination significantly...... increased the level of lymphocytic DNA damage, to an extent comparable with the effect induced by IQ. In contrast to the control group where no GST-P foci were detected, GST-P foci were detected in animals exposed to quercetin, lycopene and the combination of the two. However, the increase in the volume...

  15. The environmental monitoring of Cultural Heritage through Low Cost strategies: The frescoes of the crypt of St. Francesco d'Assisi's, Irsina (Basilicata, Southern Italy)

    Science.gov (United States)

    Sileo, Maria; Gizzi, Fabrizio; Masini, Nicola

    2015-04-01

    One of the main tools of assessment and diagnosis used to define appropriate strategies for the preservation of cultural heritage is the environmental monitoring. To achieve an environmental monitoring are needed high costs of purchase and maintenance, high costs of instrumental and for the management of the plants and processing of results. These costs imply that the technologies for environmental monitoring are not as common but their use is limited to the study very famous monuments or sites. To extend the use and dissemination of such technologies to a greater number of monuments, through the project Pro_Cult (Advanced methodological approaches and technologies for Protection and Security of Cultural Heritage) a research aimed at testing low cost technologies has been performed. The aim of the research is to develop low cost monitoring systems, assessing their effectiveness in a comparative way with commercial high cost ones. To this aim an environmental monitoring system using the Arduino system was designed and developed. It is an electronics prototyping platform based on open-source hardware and software flexible and user friendly. This system is connected to sensors for the detection of environmental parameters of non high purchase cost but with respect to the medium potential detection sensors accurately. This low cost system was tested in the framework of a microclimate monitoring project of the crypt of St. Francis of Assisi in Irsina (Southern Italy) enriched by a precious cycle of medieval frescoes. The aim of this research was to compare two monitoring systems, the first, at low cost, using Arduino system, and the second, a standard commercial product for a full yearly cycle and assess the reliability and the results obtained by the two systems. This paper shows the results of the comparative analysis of an entire monitoring yearly cycle in relation to the problems of degradation affecting the paintings of medieval crypt [1]. The obtained results

  16. Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Källman Tiia

    2005-04-01

    Full Text Available Abstract Background The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS, are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. Methods Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. Results The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. Conclusion An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals.

  17. Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

    Science.gov (United States)

    Nieminen-von Wendt, Taina; Paavonen, Juulia E; Ylisaukko-Oja, Tero; Sarenius, Susan; Källman, Tiia; Järvelä, Irma; von Wendt, Lennart

    2005-01-01

    Background The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS), are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. Methods Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. Results The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. Conclusion An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals. PMID:15826308

  18. Corneal aberration changes after rigid gas permeable contact lens wear in keratokonic patients

    Directory of Open Access Journals (Sweden)

    Fereshteh Shokrollahzadeh

    2016-12-01

    Conclusion: In this study, corneal aberrations remained unchanged 3 months after wearing RGP contact lens. Further studies with sufficient samples in different groups of keratoconus severity or baseline aberrations are needed to obtain more accurate results.

  19. Effects of intraocular lenses with different diopters on chromatic aberrations in human eye models

    National Research Council Canada - National Science Library

    Song, Hui; Yuan, Xiaoyong; Tang, Xin

    2016-01-01

    In this study, the effects of intraocular lenses (IOLs) with different diopters (D) on chromatic aberration were investigated in human eye models, and the influences of the central thickness of IOLs on chromatic aberration were compared...

  20. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    NARCIS (Netherlands)

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for

  1. An update on ECARUCA, the European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations

    NARCIS (Netherlands)

    Vulto-van Silfhout, Anneke T.; van Ravenswaaij, Conny M. A.; Hehir-Kwa, Jayne Y.; Verwiel, Eugene T. P.; Dirks, Rita; van Vooren, Steven; Schinzel, Albert; de Vries, Bert B. A.; de Leeuw, Nicole

    The European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA, www.ecaruca.net) is an online database initiated in 2003 that collects and provides detailed, curated clinical and molecular information on rare unbalanced chromosome aberrations. ECARUCA now contains

  2. Chromosomal Aberrations in Monozygotic and Dizygotic Twins Versus Singletons in Denmark During 1968-2009

    DEFF Research Database (Denmark)

    Kristensen, Lone Krøldrup; Larsen, Lisbeth A; Fagerberg, Christina

    2017-01-01

    BACKGROUND: Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could...

  3. Refractive Changes Induced by Spherical Aberration in Laser Correction Procedures: An Adaptive Optics Study.

    Science.gov (United States)

    Amigó, Alfredo; Martinez-Sorribes, Paula; Recuerda, Margarita

    2017-07-01

    To study the effect on vision of induced negative and positive spherical aberration within the range of laser vision correction procedures. In 10 eyes (mean age: 35.8 years) under cyclopegic conditions, spherical aberration values from -0.75 to +0.75 µm in 0.25-µm steps were induced by an adaptive optics system. Astigmatism and spherical refraction were corrected, whereas the other natural aberrations remained untouched. Visual acuity, depth of focus defined as the interval of vision for which the target was still perceived acceptable, contrast sensitivity, and change in spherical refraction associated with the variation in pupil diameter from 6 to 2.5 mm were measured. A refractive change of 1.60 D/µm of induced spherical aberration was obtained. Emmetropic eyes became myopic when positive spherical aberration was induced and hyperopic when negative spherical aberration was induced (R2 = 81%). There were weak correlations between spherical aberration and visual acuity or depth of focus (R2 = 2% and 3%, respectively). Contrast sensitivity worsened with the increment of spherical aberration (R2 = 59%). When pupil size decreased, emmetropic eyes became hyperopic when preexisting spherical aberration was positive and myopic when spherical aberration was negative, with an average refractive change of 0.60 D/µm of spherical aberration (R2 = 54%). An inverse linear correlation exists between the refractive state of the eye and spherical aberration induced within the range of laser vision correction. Small values of spherical aberration do not worsen visual acuity or depth of focus, but positive spherical aberration may induce night myopia. In addition, the changes in spherical refraction when the pupil constricts may worsen near vision when positive spherical aberration is induced or improve it when spherical aberration is negative. [J Refract Surg. 2017;33(7):470-474.]. Copyright 2017, SLACK Incorporated.

  4. Multispectral imaging flow cytometry reveals distinct frequencies of γ-H2AX foci induction in DNA double strand break repair defective human cell lines.

    Science.gov (United States)

    Bourton, Emma C; Plowman, Piers N; Zahir, Sheba Adam; Senguloglu, Gonul Ulus; Serrai, Hiba; Bottley, Graham; Parris, Christopher N

    2012-02-01

    The measurement of γ-H2AX foci induction in cells provides a sensitive and reliable method for the quantitation of DNA damage responses in a variety of cell types. Accurate and rapid methods to conduct such observations are desirable. In this study, we have employed the novel technique of multispectral imaging flow cytometry to compare the induction and repair of γ-H2AX foci in three human cell types with different capacities for the repair of DNA double strand breaks (DSB). A repair normal fibroblast cell line MRC5-SV1, a DSB repair defective ataxia telangiectasia (AT5BIVA) cell line, and a DNA-PKcs deficient cell line XP14BRneo17 were exposed to 2 Gy gamma radiation from a (60)Cobalt source. Thirty minutes following exposure, we observed a dramatic induction of foci in the nuclei of these cells. After 24 hrs, there was a predictable reduction on the number of foci in the MRC5-SV1 cells, consistent with the repair of DNA DSB. In the AT5BIVA cells, persistence of the foci over a 24-hr period was due to the failure in the repair of DNA DSB. However, in the DNA-PKcs defective cells (XP14BRneo17), we observed an intermediate retention of foci in the nuclei indicative of partial repair of DNA DSB. In summary, the application of imaging flow cytometry has permitted an evaluation of foci in a large number of cells (20,000) for each cell line at each time point. This provides a novel method to determine differences in repair kinetics between different cell types. We propose that imaging flow cytometry provides an alternative platform for accurate automated high through-put analysis of foci induction in a variety of cell types. Copyright © 2011 International Society for Advancement of Cytometry.

  5. Quantitative analysis of liver GST-P foci promoted by a chemical mixture of hexachlorobenzene and PCB 126: implication of size-dependent cellular growth kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yasong [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Translational Pharmacology Group, PDM, Pfizer Inc, Groton, CT (United States); Lohitnavy, Manupat; Lohitnavy, Ornrat; Eickman, Elizabeth; Gerjevic, Lisa; Yang, Raymond S.H. [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Reddy, Micaela [DMPK Group, Preclinical Sciences, Roche Palo Alto LLC, CA (United States); Ashley, Amanda [Colorado State University, Department of Cell and Molecular Biology, Fort Collins, CO (United States); Xu, Yihua [University of Wisconsin, McArdle Laboratory for Cancer Research, Madison, WI (United States); Conolly, Rory B. [USEPA, National Center for Computational Toxicology, Research Triangle Park, NC (United States)

    2008-02-15

    The objectives of this study were twofold: (1) evaluating the carcinogenic potential of the mixture of two persistent environmental pollutants, hexachlorobenzene (HCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126), in an initiation-promotion bioassay involving the development of {pi} glutathione S-transferase (GST-P) liver foci, and (2) analyzing the GST-P foci data using a biologically-based computer model (i.e., clonal growth model) with an emphasis on the effect of focal size on the growth kinetics of initiated cells. The 8-week bioassay involved a series of treatments of initiator, two-thirds partial hepatectomy, and daily oral gavage of the mixture of two doses in male F344 rats. The mixture treatment significantly increased liver GST-P foci development, indicating carcinogenic potential of this mixture. Our clonal growth model was developed to simulate the appearance and development of initiated GST-P cells in the liver over time. In the model, the initiated cells were partitioned into two subpopulations with the same division rate but different death rates. Each subpopulation was further categorized into single cells, mini- (2-11 cells), medium- (12-399 cells), and large-foci (>399 cells) with different growth kinetics. Our modeling suggested that the growth of GST-P foci is size-dependent; in general, the larger the foci, the higher the rate constants of division and death. In addition, the modeling implied that the two doses promoted foci development in different manners even though the experimental foci data appeared to be similar between the two doses. This study further illustrated how clonal growth modeling may facilitate our understanding in chemical carcinogenic process. (orig.)

  6. Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

    Directory of Open Access Journals (Sweden)

    M.V.O. Vespúcio

    2008-04-01

    Full Text Available Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH. Three groups of 32 male Wistar rats were treated as follows: group 1 (G1 had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC; G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32 did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH. Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

  7. Tropical forest restoration: tree islands as recruitment foci in degraded lands of Honduras.

    Science.gov (United States)

    Zahawi, R A; Augspurger, C K

    2006-04-01

    Tropical forest recovery in pastures is slowed by a number of biotic and abiotic factors, including a lack of adequate seed dispersal and harsh microclimatic extremes. Accordingly, methods to accelerate forest recovery must address multiple impediments. Here, we evaluated the ability of "tree islands" to serve as "recruitment foci" in a two-year study at three sites in northern Honduras. Islands of three sizes (64, 16, and 4 m2) and at two distances to secondary forest (20 and 50 m) were created by planting 2 m tall vegetative stakes of two native species: Gliricidia sepium (Fabaceae) and Bursera simaruba (Burseraceae), each in monoculture. Open-pasture "islands" of equal sizes served as controls. Tree islands reduced temperature and light (PAR) extremes as compared to open pasture, creating a microenvironment more favorable to seedling establishment. Seed-dispersing birds (quantified at one site only) showed an overwhelming preference for islands; 160 visits were recorded to islands compared with one visit to open pasture. Additionally, frugivores visited large islands more often, and for longer time periods, than small islands, thereby increasing the likelihood of a dispersal event there. In total, 144 140 seeds belonging to 186 species were collected in islands; more than 80% were grasses. Tree islands increased zoochorous tree seed rain; seed density and species richness were greater in tree islands than in open pasture, and large islands had greater seed density than smaller islands (Gliricidia only), suggesting that they are more effective for restoration. Distance to forest did not affect seed rain. A total of 543 seedlings and 41 species established in islands; > 85% were zoochorous. Seedling density did not differ among treatments (mean 0.2 seedlings/m2 for islands vs. 0.1 seedlings/m2 for pasture), although an increasing trend in tree islands over the course of two years suggests that seedling recruitment is accelerated there. Lastly, similar seedling

  8. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  9. The RBE-LET relationship for rodent intestinal crypt cell survival, testes weight loss, and multicellular spheroid cell survival after heavy-ion irradiation

    Science.gov (United States)

    Rodriguez, A.; Alpen, E. L.; Powers-Risius, P.

    1992-01-01

    This report presents data for survival of mouse intestinal crypt cells, mouse testes weight loss as an indicator of survival of spermatogonial stem cells, and survival of rat 9L spheroid cells after irradiation in the plateau region of unmodified particle beams ranging in mass from 4He to 139La. The LET values range from 1.6 to 953 keV/microns. These studies examine the RBE-LET relationship for two normal tissues and for an in vitro tissue model, multicellular spheroids. When the RBE values are plotted as a function of LET, the resulting curve is characterized by a region in which RBE increases with LET, a peak RBE at an LET value of 100 keV/microns, and a region of decreasing RBE at LETs greater than 100 keV/microns. Inactivation cross sections (sigma) for these three biological systems have been calculated from the exponential terminal slope of the dose-response relationship for each ion. For this determination the dose is expressed as particle fluence and the parameter sigma indicates effect per particle. A plot of sigma versus LET shows that the curve for testes weight loss is shifted to the left, indicating greater radiosensitivity at lower LETs than for crypt cell and spheroid cell survival. The curves for cross section versus LET for all three model systems show similar characteristics with a relatively linear portion below 100 keV/microns and a region of lessened slope in the LET range above 100 keV/microns for testes and spheroids. The data indicate that the effectiveness per particle increases as a function of LET and, to a limited extent, Z, at LET values greater than 100 keV/microns. Previously published results for spread Bragg peaks are also summarized, and they suggest that RBE is dependent on both the LET and the Z of the particle.

  10. Molecular features of colorectal polyps presenting Kudo’s type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

    Science.gov (United States)

    Shinmura, Kensuke; Konishi, Kazuo; Yamochi, Toshiko; Kubota, Yutaro; Yano, Yuichiro; Katagiri, Atsushi; Muramoto, Takashi; Kihara, Toshihiro; Tojo, Masayuki; Konda, Kenichi; Tagawa, Teppei; Yanagisawa, Fumito; Kogo, Mari; Makino, Reiko; Takimoto, Masafumi; Yoshida, Hitoshi

    2014-01-01

    Background and study aims: The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo’s type II observed by chromoendoscopy, were evaluated. Methods: The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. Results: Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P < 0.0001). No significant difference was found in the frequency of BRAF mutation among SPs apart from GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. Conclusions: Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs. PMID:26134964

  11. Image transfer with spatial coherence for aberration corrected transmission electron microscopes

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Fumio, E-mail: hosokawa@bio-net.co.jp [BioNet Ltd., 2-3-28 Nishikityo, Tachikwa, Tokyo (Japan); Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8503 (Japan); Sawada, Hidetaka [JEOL (UK) Ltd., JEOL House, Silver Court, Watchmead, Welwyn Garden City, Herts AL7 1LT (United Kingdom); Shinkawa, Takao [BioNet Ltd., 2-3-28 Nishikityo, Tachikwa, Tokyo (Japan); Sannomiya, Takumi [Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8503 (Japan)

    2016-08-15

    The formula of spatial coherence involving an aberration up to six-fold astigmatism is derived for aberration-corrected transmission electron microscopy. Transfer functions for linear imaging are calculated using the newly derived formula with several residual aberrations. Depending on the symmetry and origin of an aberration, the calculated transfer function shows characteristic symmetries. The aberrations that originate from the field’s components, having uniformity along the z direction, namely, the n-fold astigmatism, show rotational symmetric damping of the coherence. The aberrations that originate from the field’s derivatives with respect to z, such as coma, star, and three lobe, show non-rotational symmetric damping. It is confirmed that the odd-symmetric wave aberrations have influences on the attenuation of an image via spatial coherence. Examples of image simulations of haemoglobin and Si [211] are shown by using the spatial coherence for an aberration-corrected electron microscope. - Highlights: • The formula of partial coherence for aberration corrected TEM is derived. • Transfer functions are calculated with several residual aberrations. • The calculated transfer function shows the characteristic damping. • The odd-symmetric wave aberrations can cause the attenuation of image via coherence. • The examples of aberration corrected TEM image simulations are shown.

  12. Are changes in ocular aberrations with age a significant problem for refractive surgery?

    Science.gov (United States)

    Marcos, Susana

    2002-01-01

    We discuss current knowledge about the change of aberrations with aging, cataract surgery, and laser in situ keratomileusis (LASIK) for myopia. Based on this evidence, we speculate about the long-term expectations for postoperative LASIK eyes in terms of aberrations. Standard myopic LASIK surgery produces a significant increase in aberrations, particularly corneal spherical aberration, which changes to positive values. Aberrations increase with age, and in particular, the spherical aberration of the crystalline lens shifts toward positive values. Therefore, no compensatory effect is expected to occur with age after standard myopic LASIK, but rather the unusually high amount of aberrations in postoperative LASIK patients is expected to worsen with age. The amount of aberrations in patients after cataract surgery with implantation of standard intraocular lenses (IOLs) is higher than in normal young subjects. If an ideal customized ablation (not inducing aberrations and reducing naturally existing aberrations) is ever possible, the perfect correction will not last (due to the change of aberrations with age), and aberrations of the crystalline lens corrected on the cornea are likely to reappear after conventional cataract surgery. Potential benefits of customized IOLs for cataract surgery and improved optics in older patients are discussed.

  13. Photon Sieve Bandwidth Broadening by Reduction of Chromatic Aberration Effects Using Second-Stage Diffractive Optics

    Science.gov (United States)

    2015-03-26

    thesis. 25 Still another manner in which to view chromatic aberration is in terms of Lateral Chromatic Aberration ( LCA ). Eq. 18 illustrates a...wavelength in addition to the in-focus location. This difference in height of images at two different colors is LCA (21:268). Aberration Correction

  14. The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt

    KAUST Repository

    Kay, Sophie K.

    2017-03-01

    The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch’s interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes. Chemical reaction network theory (CRNT) is a powerful, generalised framework which assesses the capacity of our model for monostability or multistability, by analysing properties of the underlying network structure without recourse to specific parameter values or functional forms for reaction rates. CRNT highlights the role of β-catenin in stabilising the Notch pathway and damping oscillations, demonstrating that Wnt-mediated actions on the Hes1 promoter can induce dynamic transitions in the Notch system, from multistability to monostability. Time-dependent model simulations of cell pairs reveal the stabilising influence of Wnt upon the Notch pathway, in which β-catenin- and Dsh-mediated action on the Hes1 promoter are key in shaping the subcellular dynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notch oscillation and maintenance of fate flexibility; Wnt-mediated transcription of Hes1 favours bistability akin to cell fate selection. Cells could therefore regulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoter to coordinate the timing of cell fate selection as they migrate through the intestinal epithelium and are subject to reduced Wnt stimuli. Furthermore, mutant cells characterised by hyperstimulation of the Wnt pathway may, through coupling with Notch, invert cell fate in neighbouring healthy cells, enabling an aberrant cell to maintain

  15. The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt.

    Directory of Open Access Journals (Sweden)

    Sophie K Kay

    2017-02-01

    Full Text Available The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch's interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes. Chemical reaction network theory (CRNT is a powerful, generalised framework which assesses the capacity of our model for monostability or multistability, by analysing properties of the underlying network structure without recourse to specific parameter values or functional forms for reaction rates. CRNT highlights the role of β-catenin in stabilising the Notch pathway and damping oscillations, demonstrating that Wnt-mediated actions on the Hes1 promoter can induce dynamic transitions in the Notch system, from multistability to monostability. Time-dependent model simulations of cell pairs reveal the stabilising influence of Wnt upon the Notch pathway, in which β-catenin- and Dsh-mediated action on the Hes1 promoter are key in shaping the subcellular dynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notch oscillation and maintenance of fate flexibility; Wnt-mediated transcription of Hes1 favours bistability akin to cell fate selection. Cells could therefore regulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoter to coordinate the timing of cell fate selection as they migrate through the intestinal epithelium and are subject to reduced Wnt stimuli. Furthermore, mutant cells characterised by hyperstimulation of the Wnt pathway may, through coupling with Notch, invert cell fate in neighbouring healthy cells, enabling an aberrant

  16. Calibration results using highly aberrated images for aligning the JWST instruments to the telescope

    Science.gov (United States)

    Smith, Koby Z.; Acton, D. Scott; Gallagher, Ben B.; Knight, J. Scott; Dean, Bruce H.; Jurling, Alden S.; Zielinski, Thomas P.

    2016-07-01

    mostly of 3rd-order astigmatism and coma. This is because the elliptical tertiary mirror of the AOS is used off of its ideal foci locations without the compensating wavefront effects of the JWST primary and secondary mirrors. Therefore, the PSFs created are highly asymmetric with relatively complex structure and the centroid and encircled energy analyses traditionally used to locate images are not sufficient for ensuring the AOS to ISIM alignment. A novel approach combining phase retrieval and spatial metrology was developed to both locate the images with respect to the AOS and provide calibration information for eventual AOS to ISIM alignment verification. During final JWST OTE and ISIM (OTIS) testing, only a single thru-focus image will be collected by the instruments. Therefore, tools and processes were developed to perform single-image phase retrieval on these highly aberrated images such that any single image of the ASPA source can provide calibrated knowledge of the instruments' position relative to the AOS. This paper discusses the results of the methodology, hardware, and calibration performed to ensure that the AOS and ISIM are aligned within their respective tolerances at JWST OTIS testing.

  17. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  18. Deep Tissue Wavefront Estimation for Sensorless Aberration Correction

    Directory of Open Access Journals (Sweden)

    Ibrahimovic Emina

    2015-01-01

    Full Text Available The multiple light scattering in biological tissues limits the measurement depth for traditional wavefront sensor. The attenuated ballistic light and the background noise caused by the diffuse light give low signal to noise ratio for wavefront measurement. To overcome this issue, we introduced a wavefront estimation method based on a ray tracing algorithm to overcome this issue. With the knowledge of the refractive index of the medium, the wavefront is estimated by calculating optical path length of rays from the target inside of the samples. This method can provide not only the information of spherical aberration from the refractive-index mismatch between the medium and biological sample but also other aberrations caused by the irregular interface between them. Simulations based on different configurations are demonstrated in this paper.

  19. Membrane-based aberration-corrected tunable micro-lenses

    Science.gov (United States)

    Waibel, Philipp; Ermantraut, Eugen; Mader, Daniel; Zappe, Hans; Seifert, Andreas

    2010-05-01

    We present measurements and simulations of membrane-based micro-lens stacks, tunable in focal length in the range of 10mm to 50mm without chromatic aberration. The pressure-actuated, liquid-filled, membrane-based micro-lenses are fabricated by an all-silicone molding approach and consist of three chambers separated by two highly flexible silicone-membranes. Based on the idea of the classical achromatic Fraunhofer doublet, two different liquids with suitable optical properties are used. Pressure-dependent surface topologies are measured by profilometry for determining the correlation between refraction and applied pressure. The profiles are fit to polynomials; the coefficients of the polynomials are pressure-dependent and fit to empirically determined functions which are then used as an input for optical ray-tracing. Using this approach, the focal length is tunable while compensating for chromatic aberration by suitably applied pressures.

  20. Aberrations and adaptive optics in super-resolution microscopy

    Science.gov (United States)

    Booth, Martin; Andrade, Débora; Burke, Daniel; Patton, Brian; Zurauskas, Mantas

    2015-01-01

    As one of the most powerful tools in the biological investigation of cellular structures and dynamic processes, fluorescence microscopy has undergone extraordinary developments in the past decades. The advent of super-resolution techniques has enabled fluorescence microscopy – or rather nanoscopy – to achieve nanoscale resolution in living specimens and unravelled the interior of cells with unprecedented detail. The methods employed in this expanding field of microscopy, however, are especially prone to the detrimental effects of optical aberrations. In this review, we discuss how super-resolution microscopy techniques based upon single-molecule switching, stimulated emission depletion and structured illumination each suffer from aberrations in different ways that are dependent upon intrinsic technical aspects. We discuss the use of adaptive optics as an effective means to overcome this problem. PMID:26124194

  1. Aberration characteristics of plane-parallel compensator plate

    Science.gov (United States)

    Komarova, I. E.

    1984-02-01

    A specially constructed plane parallel compensator plate in a ring telescope catodioptric objective does not affect the size of the dead zone in the pupil and will not only eliminate parasitic flare or bright spots but also allow the relative aperture of each mirror and of the entire objective to be substantially enlarged. Such a plate consists of two elements, the smaller one with a diameter equal to that of the secondary mirror placed at the center of the larger one so as to face that mirror. Here the aberration characteristics of this compensator are analyzed according to the laws of geometric optics for wide beams of light rays. Five different compensator configurations are conceived on this basis for complete correction of spherical aberration, with the appropriate formulas given for calculating the necessary plate thickness.

  2. [Aberration of somatic karyotype in normozoospermic males from infertile couples].

    Science.gov (United States)

    Mordalska, A; Barczyk, A; Hübner, H; Malinowski, A; Szpakowski, M

    1998-06-01

    During the complex investigation of couple infertility, a group of 40 normozoospermic males having low density of semen was selected. Cytogenetic analysis revealed 2 cases of somatic karyotype aberrations: 47,XYY and 46,XY,t(14;19), and 2 cases of chromosomal polymorphisms: 46,XYq+ i 46,XY,14p+. In the article the mechanism of fertility disturbances evoked by these findings is discussed in aspects of the function of spermatozoa and its genetic material content.

  3. Hybridoma fusion cell lines contain an aberrant kappa transcript.

    Science.gov (United States)

    Carroll, W L; Mendel, E; Levy, S

    1988-10-01

    The V region sequence of a non-productive kappa transcript from two myeloma fusion partners has been determined. This transcript has an aberrant VJ recombination site resulting in a translation stop site at position 105. It is variably expressed in hybridomas made from all fusion partners derived from the original MOPC-21 tumor. The amount of this transcript may greatly exceed levels of the productive light chain mRNA.

  4. Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

    OpenAIRE

    Wu, June K.; Christopher Kitajewski; Maia Reiley; Keung, Connie H.; Julie Monteagudo; Andrews, John P.; Peter Liou; Arul Thirumoorthi; Alvin Wong; Kandel, Jessica J; Shawber, Carrie J.

    2015-01-01

    Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial...

  5. Aberrant Phenotype in Iranian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mehdi Jahedi

    2014-03-01

    Full Text Available Purpose: The aim of this study was to evaluate the incidence of aberrant phenotypes and possible prognostic value in peripheral and bone marrow blood mononuclear cells of Iranian patients with AML. Methods: 56 cases of de novo AML (2010-2012 diagnosed by using an acute panel of monoclonal antibodies by multiparametric flowcytometry. Immunophenotyping was done on fresh bone marrow aspirate and/or peripheral blood samples using the acute panel of MoAbs is stained with Phycoerythrin (PE /fluorescein isothiocyanate (FITC, Allophycocyanin (APC and Peridinin-chlorophyll protein complex (perCP. We investigated Co-expression of lymphoid-associated markers CD2, CD3, CD7, CD 10, CD19, CD20 and CD22 in myeloblasts. Results: Out of the 56 cases, 32 (57.1% showed AP. CD7 was positive in 72.7% of cases in M1 and 28.5% in M2 but M3 and M4 cases lacked this marker. We detected CD2 in 58.35 of M1cases, 21.40% of M2 cases, 33.3 of M3 and 20% of M5; but M4 patients lacked this marker. The CBC analysis demonstrated a wide range of haemoglobin concentration, Platelet and WBC count which varied from normal to anaemia, thrombocytopenia to thrombocytosis and leukopenia to hyper leukocytosis. Conclusions: Our findings showed that CD7 and CD2 were the most common aberrant marker in Iranian patients with AML. However, we are not find any significant correlation between aberrant phenotype changing and MRD in our population. Taken together, this findings help to provide new insights in to the investigation of other aberrant phenotypes that may play roles in diagnosis and therapeutic of AML.

  6. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  7. Aberration correction for time-domain ultrasound diffraction tomography

    Science.gov (United States)

    Mast, T. Douglas

    2002-07-01

    Extensions of a time-domain diffraction tomography method, which reconstructs spatially dependent sound speed variations from far-field time-domain acoustic scattering measurements, are presented and analyzed. The resulting reconstructions are quantitative images with applications including ultrasonic mammography, and can also be considered candidate solutions to the time-domain inverse scattering problem. Here, the linearized time-domain inverse scattering problem is shown to have no general solution for finite signal bandwidth. However, an approximate solution to the linearized problem is constructed using a simple delay-and-sum method analogous to "gold standard" ultrasonic beamforming. The form of this solution suggests that the full nonlinear inverse scattering problem can be approximated by applying appropriate angle- and space-dependent time shifts to the time-domain scattering data; this analogy leads to a general approach to aberration correction. Two related methods for aberration correction are presented: one in which delays are computed from estimates of the medium using an efficient straight-ray approximation, and one in which delays are applied directly to a time-dependent linearized reconstruction. Numerical results indicate that these correction methods achieve substantial quality improvements for imaging of large scatterers. The parametric range of applicability for the time-domain diffraction tomography method is increased by about a factor of 2 by aberration correction. copyright 2002 Acoustical Society of America.

  8. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  9. Nutritional rehabilitation of mitochondrial aberrations in aplastic anaemia.

    Science.gov (United States)

    He, Ling; Miao, Xiaoyan; Lv, Guangyan; Yang, Peiman; Wu, Wenguo; Jia, Li

    2011-04-01

    Aplastic anaemia (AA) is a disease characterised by bone marrow hypocellularity and peripheral blood pancytopenia. AA is also associated with mitochondrial aberrations. The present study was undertaken primarily to test the hypothesis that a nutrient mixture could affect the nutritional rehabilitation of mitochondrial aberrations in AA mice. BALB/c AA mice were induced by a combination of hypodermic injections of acetylphenylhydrazine (100 mg/kg), X-rays (2·0 Gy) and intraperitoneal injections of cyclophosphamide (80 mg/kg). We treated these mice with nutrient mixture-supplemented diets in a dose-dependent manner (1445·55, 963·7, 674·59 mg/kg per d), and the effects of the nutrient mixture for mitochondrial rehabilitation were analysed in AA mice. Transmission electron microscopy showed that mitochondrial ultrastructural abnormalities in bone marrow cells, splenocytes and hepatocytes of the nutrient mixture groups were restored markedly, compared with the AA group. Mitochondrial membrane potentials of the nutrient mixture groups were increased remarkably. Western blot analysis also revealed that the nutrient mixture significantly inhibited cytochrome c release of mitochondria in the AA group. Furthermore, the mitochondrial DNA content of the nutrient mixture groups was also increased. Our data suggest that the nutrient mixture may promote the rehabilitation of mitochondrial aberrations, and consequently protects against mitochondrial dysfunction in AA mice.

  10. Aberrant behavior and cognitive ability in preschool children

    Directory of Open Access Journals (Sweden)

    Bala Gustav

    2007-01-01

    Full Text Available The sample included 712 preschool boys and girls at the age of 4 to 7 years (mean 5.96 decimal years and standard deviation .96 from preschool institutions in Novi Sad, Sombor, Sremska Mitrovica and Bačka Palanka. Information concerning 36 indicators of aberrant behavior of the children were supplied by their parents, whereas their cognitive ability was tested by Raven’s progressive colored matrices. Based on factor analysis (promax method, four factors i.e. generators of aberrant behavior in children were singled out: aggression, anxiousness, dissociation, and hysteria, whose relations with cognitive functioning and age were also analyzed by factor analysis. Aberrant behavior and cognitive abilities show significant interrelatedness. Owing to orderly developed cognitive abilities, a child understands essence and reality of problems, realizes possibilities and manners of solving them, and succeeds in realizing successful psycho-social functioning. Developed cognitive abilities enable a child to recognize and understand her/his own reactions in different situations and develop manners of reacting, which leads to strengthening psycho-social safety and adapting behavior in accordance with her/his age and abilities.

  11. Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

    Science.gov (United States)

    Zarroug, Isam M A; Hashim, Kamal; Elaagip, Arwa H; Samy, Abdallah M; Frah, Ehab A; ElMubarak, Wigdan A; Mohamed, Hanan A; Deran, Tong Chor M; Aziz, Nabil; Higazi, Tarig B

    2016-01-01

    The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs. A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests. Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There

  12. Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

    Directory of Open Access Journals (Sweden)

    Isam M A Zarroug

    Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to

  13. Correction method of wavefront aberration on signal quality in holographic memory

    Science.gov (United States)

    Kimura, Eri; Nakajima, Akihito; Akieda, Kensuke; Ohori, Tomohiro; Katakura, Kiyoto; Kondo, Yo; Yamamoto, Manabu

    2011-02-01

    One of the problems that affects the practical use of holographic memory is deterioration of the reproduced images due to aberration in the optical system. The medium must be interchangeable, and hence it is necessary to clarify the influence of aberration in the optical system on the signal quality and perform aberration correction for drive compatibility. In this study, aberration is introduced in the reference light beam during image reproduction, and the deterioration of the reproduced image signal is examined. In addition, for a basic study of aberration correction, the correction technique using a two-dimensional signal processing is studied.

  14. Temporal and spatial distribution characteristics in the natural plague foci of Chinese Mongolian gerbils based on spatial autocorrelation.

    Science.gov (United States)

    Du, Hai-Wen; Wang, Yong; Zhuang, Da-Fang; Jiang, Xiao-San

    2017-08-07

    The nest flea index of Meriones unguiculatus is a critical indicator for the prevention and control of plague, which can be used not only to detect the spatial and temporal distributions of Meriones unguiculatus, but also to reveal its cluster rule. This research detected the temporal and spatial distribution characteristics of the plague natural foci of Mongolian gerbils by body flea index from 2005 to 2014, in order to predict plague outbreaks. Global spatial autocorrelation was used to describe the entire spatial distribution pattern of the body flea index in the natural plague foci of typical Chinese Mongolian gerbils. Cluster and outlier analysis and hot spot analysis were also used to detect the intensity of clusters based on geographic information system methods. The quantity of M. unguiculatus nest fleas in the sentinel surveillance sites from 2005 to 2014 and host density data of the study area from 2005 to 2010 used in this study were provided by Chinese Center for Disease Control and Prevention. The epidemic focus regions of the Mongolian gerbils remain the same as the hot spot regions relating to the body flea index. High clustering areas possess a similar pattern as the distribution pattern of the body flea index indicating that the transmission risk of plague is relatively high. In terms of time series, the area of the epidemic focus gradually increased from 2005 to 2007, declined rapidly in 2008 and 2009, and then decreased slowly and began trending towards stability from 2009 to 2014. For the spatial change, the epidemic focus regions began moving northward from the southwest epidemic focus of the Mongolian gerbils from 2005 to 2007, and then moved from north to south in 2007 and 2008. The body flea index of Chinese gerbil foci reveals significant spatial and temporal aggregation characteristics through the employing of spatial autocorrelation. The diversity of temporary and spatial distribution is mainly affected by seasonal variation, the human

  15. The p150 subunit of CAF-1 causes association of SUMO2/3 with the DNA replication foci

    Energy Technology Data Exchange (ETDEWEB)

    Uwada, Junsuke [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Tanaka, Niina; Yamaguchi, Yutaro; Uchimura, Yasuhiro [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Shibahara, Kei-ichi [Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima (Japan); Nakao, Mitsuyoshi [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan)

    2010-01-01

    The small ubiquitin-related modifier 2/3 (SUMO2/3) can be post-translationally conjugated to a wide variety of proteins constituting chromatin, the platform for genetic and epigenetic regulation. Nevertheless, it is unclear how SUMO2/3 and SUMO2/3-modified proteins are delivered to the chromatin fibers. Here we report that the largest subunit of chromatin assembly factor 1 (CAF-1), human p150, interacts directly and preferentially with SUMO2/3. Amino acid residue of 98-105 in p150 is essential and sufficient for SUMO2/3 interaction. p150-SUMO2/3 interaction coincided with regions that replicate chromatin fibers, because accumulation of the proliferating cell nuclear antigen (PCNA), and incorporation of bromodeoxyuridine (BrdU) were detected at foci co-localized with both p150 and SUMO2/3 during the S-phase in a cell line expressing epitope-tagged p150. Although inhibition of SUMO2/3 expression had only a small effect on p150 deposition on the replication sites, depletion of p150 led to delocalization of SUMO2/3 from the replication foci. Furthermore, p150 mutants deficient in SUMO2/3 interaction, caused a major reduction of SUMO2/3 at the replication foci. Thus, our findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication.

  16. Hidden sylvatic foci of the main vector of Chagas disease Triatoma infestans: threats to the vector elimination campaign?

    Directory of Open Access Journals (Sweden)

    Leonardo A Ceballos

    2011-10-01

    Full Text Available Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs. Triatoma infestans, traditionally considered to be limited to domestic or peridomestic (abbreviated as D/PD habitats throughout most of its range, is the target of an elimination program that has achieved limited success in the Gran Chaco region in South America.During a two-year period we conducted semi-annual searches for triatomine bugs in every D/PD site and surrounding sylvatic habitats after full-coverage spraying of pyrethroid insecticides of all houses in a well-defined rural area in northwestern Argentina. We found six low-density sylvatic foci with 24 T. infestans in fallen or standing trees located 110-2,300 m from the nearest house or infested D/PD site detected after insecticide spraying, when house infestations were rare. Analysis of two mitochondrial gene fragments of 20 sylvatic specimens confirmed their species identity as T. infestans and showed that their composite haplotypes were the same as or closely related to D/PD haplotypes. Population studies with 10 polymorphic microsatellite loci and wing geometric morphometry consistently indicated the occurrence of unrestricted gene flow between local D/PD and sylvatic populations. Mitochondrial DNA and microsatellite sibship analyses in the most abundant sylvatic colony revealed descendents from five different females. Spatial analysis showed a significant association between two sylvatic foci and the nearest D/PD bug population found before insecticide spraying.Our study shows that, despite of its high degree of domesticity, T. infestans has sylvatic colonies with normal chromatic characters (not melanic morphs highly connected to D/PD conspecifics in the Argentinean Chaco. Sylvatic habitats may provide a transient or permanent refuge after control interventions, and function as sources for D/PD reinfestation. The occurrence of sylvatic foci of T. infestans in

  17. DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

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    Nadine Schuler

    Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

  18. Early p53-positive foci as indicators of tumor risk in ultraviolet-exposed hairless mice: kinetics of induction, effects of DNA repair deficiency, and p53 heterozygosity.

    Science.gov (United States)

    Rebel, H; Mosnier, L O; Berg, R J; Westerman-de Vries, A; van Steeg, H; van Kranen, H J; de Gruijl, F R

    2001-02-01

    p53 mutations appear to be early events in skin carcinogenesis induced by chronic UVB irradiation. Clusters of epidermal cells that express p53 in mutant conformation ("p53 positive foci") are easily detected by immunohistochemical staining long before the appearance of skin carcinomas or their precursor lesions. In a hairless mouse model, we determined the dose-time dependency of the induction of these p53+ foci and investigated the relationship with the induction of skin carcinomas. The density of p53+ foci may be a good direct indicator of tumor risk. Hairless SKH1 mice were exposed to either of two regimens of daily UVB (500 or 250 J/m2 broadband UV from Philips TL12 lamps; 54% UVB 280-315 nm). With the high-dose regimen, the average number of p53+ foci in a dorsal skin area (7.2 cm2) increased rapidly from 9.0 +/- 2.1 (SE) at 15 days to 470 +/- 80 (SE) at 40 days. At half that daily dose, the induction of p53+ foci was slower by a factor of 1.49 +/- 0.15, very similar to a previously observed slower induction of squamous cell carcinomas by a factor of 1.54 +/- 0.02. In a double-log plot of the average number of p53 + foci versus time, the curves for the two exposure regimens ran parallel (slope, 3.7 +/- 0.7), similar to the curves for the number of tumors versus time (slope, 6.9 +/- 0.8). The difference in slopes (3.7 versus 6.9) is in line with the contention that more rate-limiting steps are needed to develop a tumor than a p53+ focus. By the time the first tumors appear (around 7-8 weeks with the high daily dose), the dorsal skin contains >100 p53+ foci/cm2. To further validate the density of p53+ foci as a direct measure of tumor risk, we carried out experiments with transgenic mice with an enhanced susceptibility to UV carcinogenesis, homozygous Xpa knockout mice (deficient in nucleotide excision repair) and heterozygousp53 knockout mice (i.a. partially deficient in apoptosis). In both of these cancer-prone strains, the p53+ foci were induced at markedly

  19. Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal.

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    Lamine Diawara

    2009-07-01

    Full Text Available Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas.Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000.This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional objective to assess progress towards elimination endpoints in all

  20. Myofibroblastoma of the Female Breast with Admixed but Distinct Foci of Spindle Cell Lipoma: A Case Report

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    Hazem A. H. Ibrahim

    2013-01-01

    Full Text Available Mammary myofibroblastoma (MFB is a rare benign spindle neoplasm that affects both sexes with a male predominance. It can exhibit a wide range of histological patterns. We report a case of epithelioid/spindle MFB of the female breast with admixed, but distinct, foci of spindle cell lipoma. Whilst all the spindle cells within the tumour expressed CD34, AR, ER, BCL2, and CD10, only those within the myofibroblastoma expressed desmin and only those within the lipomatous areas expressed S100. This finding, to our knowledge, is a novel one that has not been reported before.

  1. Myofibroblastoma of the female breast with admixed but distinct foci of spindle cell lipoma: a case report.

    Science.gov (United States)

    Ibrahim, Hazem A H; Shousha, Sami

    2013-01-01

    Mammary myofibroblastoma (MFB) is a rare benign spindle neoplasm that affects both sexes with a male predominance. It can exhibit a wide range of histological patterns. We report a case of epithelioid/spindle MFB of the female breast with admixed, but distinct, foci of spindle cell lipoma. Whilst all the spindle cells within the tumour expressed CD34, AR, ER, BCL2, and CD10, only those within the myofibroblastoma expressed desmin and only those within the lipomatous areas expressed S100. This finding, to our knowledge, is a novel one that has not been reported before.

  2. [Additional evidence for the species composition of mosquitoes (Diptera, Psichodidae, Phlebotominae) in the visceral leishmaniasis foci of Uzbekistan].

    Science.gov (United States)

    Fatullaeva, A A; Kovalenko, D A; Baranets, M S; Ponirovskiĭ, E N

    2014-01-01

    The species composition of mosquitoes was studied in the foci of visceral leishmaniasis in the Navoiy and Samarkand Provinces of Uzbekistan. The human settlements where these observations were made were located at 1000-1200 m above sea level. Seven species: Phlebotomus sergenti, P. caucasicus, P. longiductus, P. papatasi, P. alexandri, Sergetomyia sumbarica, and S. grecovi were found. The predominant species was P. sergenti; P. longiductus was a vector for visceral leishmaniasis, which was present in all the collected samples. Bovine animal and small cattle yards were ascertained to be the hatching of mosquito eggs.

  3. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification.

    Science.gov (United States)

    Wilson, Korey A; Elefanty, Andrew G; Stanley, Edouard G; Gilbert, David M

    2016-09-16

    Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification.

  4. Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

    Science.gov (United States)

    Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

    2007-01-01

    We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

  5. Frugivorous birds influence the spatial organization of tropical forests through the generation of seedling recruitment foci under zoochoric trees

    Science.gov (United States)

    Trolliet, Franck; Forget, Pierre-Michel; Doucet, Jean-Louis; Gillet, Jean-François; Hambuckers, Alain

    2017-11-01

    Animal-mediated seed dispersal is recognized to influence the spatial organization of plant communities but little is known about how frugivores cause such patterns. Here, we explored the role of hornbills and primates in generating recruitment foci under two zoochoric trees, namely Staudtia kamerunensis (Myristicaceae) and Dialium spp. (Fabaceae - Caesalpiniodea) in a forest-savanna mosaic landscape in D.R. Congo. We also examined the influence of the availability of fruits in the neighborhood and the amount of forest cover in the landscape on such clumping patterns. The density and species richness of hornbill-dispersed and the density of primate-dispersed seedlings were significantly higher under Staudtia kamerunensis trees than at control locations. However, we did not find such patterns under Dialium spp. trees compared to control locations except for the density of hornbill-dispersed seedlings which was lower at control locations. Also, we found that an increasing amount of forest cover in the landscape was associated with an increase in the density of hornbill-dispersed seedlings, although the tendency was weak (R2 = 0.065). We concluded that S. kamerunensis acts as a recruitment foci and plays a structuring role in Afrotropical forests. Hornbills were probably the main frugivore taxon responsible for the clumping under that tree and appear as a key ecological component in fragmented and disturbed landscapes where the diversity of large frugivores such as primates is reduced. Our findings improve our understanding of the causal mechanisms responsible for the spatial organization of tropical forests.

  6. Aberration-Coreected Electron Microscopy at Brookhaven National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Zhu,Y.; Wall, J.

    2008-04-01

    The last decade witnessed the rapid development and implementation of aberration correction in electron optics, realizing a more-than-70-year-old dream of aberration-free electron microscopy with a spatial resolution below one angstrom [1-9]. With sophisticated aberration correctors, modern electron microscopes now can reveal local structural information unavailable with neutrons and x-rays, such as the local arrangement of atoms, order/disorder, electronic inhomogeneity, bonding states, spin configuration, quantum confinement, and symmetry breaking [10-17]. Aberration correction through multipole-based correctors, as well as the associated improved stability in accelerating voltage, lens supplies, and goniometers in electron microscopes now enables medium-voltage (200-300kV) microscopes to achieve image resolution at or below 0.1nm. Aberration correction not only improves the instrument's spatial resolution but, equally importantly, allows larger objective lens pole-piece gaps to be employed thus realizing the potential of the instrument as a nanoscale property-measurement tool. That is, while retaining high spatial resolution, we can use various sample stages to observe the materials response under various temperature, electric- and magnetic- fields, and atmospheric environments. Such capabilities afford tremendous opportunities to tackle challenging science and technology issues in physics, chemistry, materials science, and biology. The research goal of the electron microscopy group at the Dept. of Condensed Matter Physics and Materials Science and the Center for Functional Nanomaterials, as well as the Institute for Advanced Electron Microscopy, Brookhaven National Laboratory (BNL), is to elucidate the microscopic origin of the physical- and chemical-behavior of materials, and the role of individual, or groups of atoms, especially in their native functional environments. We plan to accomplish this by developing and implementing various quantitative

  7. Trypanosoma vivax, T. congolense “forest type” and T. simiae: prevalence in domestic animals of sleeping sickness foci of Cameroon

    Science.gov (United States)

    Nimpaye, H.; Njiokou, F.; Njine, T.; Njitchouang, G.R.; Cuny, G.; Herder, S.; Asonganyi, T.; Simo, G.

    2011-01-01

    In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense “forest type”, and T. simiae) infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon. The polymerase chain reaction (PCR) based method was used to identify these trypanosome species. A total of 237 (27.08%) domestic animals were infected by at least one trypanosome species. The prevalence of T. vivax, T. congolense “forest type” and T. simiae were 20.91%, 11.42% and 0.34% respectively. The prevalences of T. vivax and T. congolense “forest type” differed significantly between the animal species and between the foci (p < 0.0001); however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study. The high prevalences of T. vivax and T. congolense “forest type” in Bipindi and Fontem-Center indicate their intense transmission in these foci. PMID:21678793

  8. Aberrant expression of long noncoding RNAs in autistic brain.

    Science.gov (United States)

    Ziats, Mark N; Rennert, Owen M

    2013-03-01

    The autism spectrum disorders (ASD) have a significant hereditary component, but the implicated genetic loci are heterogeneous and complex. Consequently, there is a gap in understanding how diverse genomic aberrations all result in one clinical ASD phenotype. Gene expression studies from autism brain tissue have demonstrated that aberrantly expressed protein-coding genes may converge onto common molecular pathways, potentially reconciling the strong heritability and shared clinical phenotypes with the genomic heterogeneity of the disorder. However, the regulation of gene expression is extremely complex and governed by many mechanisms, including noncoding RNAs. Yet no study in ASD brain tissue has assessed for changes in regulatory long noncoding RNAs (lncRNAs), which represent a large proportion of the human transcriptome, and actively modulate mRNA expression. To assess if aberrant expression of lncRNAs may play a role in the molecular pathogenesis of ASD, we profiled over 33,000 annotated lncRNAs and 30,000 mRNA transcripts from postmortem brain tissue of autistic and control prefrontal cortex and cerebellum by microarray. We detected over 200 differentially expressed lncRNAs in ASD, which were enriched for genomic regions containing genes related to neurodevelopment and psychiatric disease. Additionally, comparison of differences in expression of mRNAs between prefrontal cortex and cerebellum within individual donors showed ASD brains had more transcriptional homogeneity. Moreover, this was also true of the lncRNA transcriptome. Our results suggest that further investigation of lncRNA expression in autistic brain may further elucidate the molecular pathogenesis of this disorder.

  9. Effective object planes for aberration-corrected transmission electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, R., E-mail: ryu@tsinghua.edu.cn [Beijing National Center for Electron Microscopy and Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Lentzen, M. [Institute of Solid State Research and Ernst Ruska Centre, Research Centre Juelich, 52425 Juelich (Germany); Zhu, J. [Beijing National Center for Electron Microscopy and Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2012-01-15

    In aberration-corrected transmission electron microscopy, the image contrast depends sensitively on the focus value. With the point resolution extended to an information limit of below 0.1 nm, even a focus change of as small as one nanometer could give a significant change in image contrast. Therefore, it is necessary to consider in detail the optimum focus condition in order to take full advantage of aberration-correction. In this study, the thickness dependence of the minimum contrast focus has been investigated by dynamical image simulations for amorphous model structures of carbon, germanium, and tungsten, which were constructed by molecular dynamics simulations. The calculation results show that the minimum contrast focus varies with the object thickness, supporting the use of an effective object plane close to the midplane instead of the exit plane of a sample, as suggested by Bonhomme and Beorchia [J. Phys. D: Appl. Phys. 16, 705 (1983)] and Lentzen [Microscopy and Microanalysis 12, 191 (2006)]. Thus supported particles and wedge-shaped crystals with symmetrical top and bottom surfaces could be imaged at a focus condition independent of the uneven bottom face. Image simulations of crystalline samples as a function of focus and thickness show: for an object thickness of less than 10 nm, the optimum focus condition is matched better if the midplane of the object, instead of the exit plane, is chosen as reference plane. -- Highlights: Black-Right-Pointing-Pointer Stringent focus condition is required for aberration-corrected TEM. Black-Right-Pointing-Pointer Optimum focus should be set with respect to the midplane of a sample. Black-Right-Pointing-Pointer The focus condition could be independent of the lateral position on a wedged sample.

  10. The effects of chalazion excision on corneal surface aberrations.

    Science.gov (United States)

    Park, Young Min; Lee, Jong Soo

    2014-10-01

    This study is the first to consider the effects of chalazion on corneal surface aberrations taking into account of corneal zones, and to establish the size standard for the excision of chalazion. Twenty three eyes from 23 patients with central upper eyelid chalazion larger than 3mm were recruited in this prospective study. The participants were classified into two groups, depending on size of the lesion: Group 1 with lesion size 3-5mm and Group 2 with lesion size >5mm Chalazion was excised by standard transconjunctival vertical incision. Corneal surface aberrations were measured using a Galilei™ analyzer and an auto-refractometer before and 2 months after the excision. Corneal astigmatism in all patients decreased significantly in both auto refractometer (P=0.012) and Galilei™ (P=0.020) measurements after chalazion excision. RMS of total HOAs decreased significantly in 6mm (P=0.043) and 3mm zone (P=0.051). The RMS of Zernike orders in the vertical and horizontal trefoil decreased significantly in 6mm (P=0.035) and 3mm (P=0.041) zone. Group 2 showed a significant decrease in corneal astigmatism in both auto refractometer (P=0.040) and Galilei™ (P=0.017) parameters after chalazion excision. Group 1 showed an insignificant decrease in corneal astigmatism. Unlike Group 1, the RMS of total HOAs and vertical and horizontal trefoil in 6mm zone decreased significantly in Group 2 (Pchalazion increases astigmatism and HOAs, especially at the peripheral cornea. Significantly induced astigmatism and HOAs are caused by chalazion >5mm in size. Thus, we recommend the surgical excision of chalazion >5mm in size to reduce corneal surface aberrations. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  11. Theory of aberration fields for general optical systems with freeform surfaces.

    Science.gov (United States)

    Fuerschbach, Kyle; Rolland, Jannick P; Thompson, Kevin P

    2014-11-03

    This paper utilizes the framework of nodal aberration theory to describe the aberration field behavior that emerges in optical systems with freeform optical surfaces, particularly φ-polynomial surfaces, including Zernike polynomial surfaces, that lie anywhere in the optical system. If the freeform surface is located at the stop or pupil, the net aberration contribution of the freeform surface is field constant. As the freeform optical surface is displaced longitudinally away from the stop or pupil of the optical system, the net aberration contribution becomes field dependent. It is demonstrated that there are no new aberration types when describing the aberration fields that arise with the introduction of freeform optical surfaces. Significantly it is shown that the aberration fields that emerge with the inclusion of freeform surfaces in an optical system are exactly those that have been described by nodal aberration theory for tilted and decentered optical systems. The key contribution here lies in establishing the field dependence and nodal behavior of each freeform term that is essential knowledge for effective application to optical system design. With this development, the nodes that are distributed throughout the field of view for each aberration type can be anticipated and targeted during optimization for the correction or control of the aberrations in an optical system with freeform surfaces. This work does not place any symmetry constraints on the optical system, which could be packaged in a fully three dimensional geometry, without fold mirrors.

  12. Aberrant microRNA expression in multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, Konstantinos; Gimsing, Peter; Grønbæk, Kirsten

    2013-01-01

    Multiple myeloma (MM) is a devastating disease with a complex biology, and in spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post......-transcriptional level. More than half of all protein coding genes are estimated to be controlled by miRNAs, and their expression is frequently deregulated in many diseases, including cancer. Recent studies have reported aberrant miRNA expression patterns in MM, and the function of individual miRNAs in MM has been...

  13. Chromosomal aberrations and SCEs as biomarkers of cancer risk

    DEFF Research Database (Denmark)

    Norppa, H; Bonassi, S; Hansteen, I-L

    2006-01-01

    Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European...... collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time...

  14. Genome-wide identification of significant aberrations in cancer genome

    Directory of Open Access Journals (Sweden)

    Yuan Xiguo

    2012-07-01

    Full Text Available Abstract Background Somatic Copy Number Alterations (CNAs in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC, a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1 exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2 performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3 iteratively detecting Significant Copy Number Aberrations (SCAs and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma. When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC or tumor suppressor genes (e.g., CDKN2A/B. Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes

  15. Resistant carbohydrates stimulate cell proliferation and crypt fission in wild-type mice and in the Apc(Min/+) mouse model of intestinal cancer, association with enhanced polyp development.

    Science.gov (United States)

    Mandir, Nikki; Englyst, Hans; Goodlad, Robert A

    2008-10-01

    Fermentation of carbohydrates in the colon can stimulate cell proliferation and could thus be a cancer risk. The effects of resistant carbohydrates, i.e. those not digested and absorbed in the small intestine, on cell proliferation, crypt fission and polyp development were investigated in wild-type and adenomatous polyposis coli multiple intestinal neoplasia (Apc(Min/+)) mice. Fifteen 4-week-old female wild-type and fifteen Apc(Min/+) mice were used for each group and fed a chow diet, a semi-synthetic diet or the semi-synthetic supplemented with wheat bran or an apple pomace preparation, both high in resistant carbohydrates, for 8 weeks. Tissue from all mice was used to measure cell proliferation and crypt fission and tissue from the Apc(Min/+) mice was scored for polyp number and tumour burden. There were slight reductions in intestinal mass in the mice fed the semi-synthetic diets and this was increased by the inclusion of resistant carbohydrates. The Apc(Min/+) mice had elevated cell proliferation and crypt fission in the distal small intestine and colon and these were increased by the resistant carbohydrates. Bran or apple pomace significantly increased polyp number in the proximal third of the small intestine. Apple pulp more than doubled polyp number throughout the small bowel (99.2 (SEM 11.1) v. 40.0 (SEM 8.2), Ptypes of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission.

  16. Aberrant activity in degenerated retinas revealed by electrical imaging

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    Günther eZeck

    2016-02-01

    Full Text Available In this review I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL of rod-degenerated (rd mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs and local field potentials reflecting strong trans-membrane currents within the GCL. RGCs in rod-degenerated retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm-generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic local field potentials (LFP manifested as spatially-restricted low-frequency (5–15 Hz voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap-junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies.

  17. Harmonic source wavefront aberration correction for ultrasound imaging

    Science.gov (United States)

    Dianis, Scott W.; von Ramm, Olaf T.

    2011-01-01

    A method is proposed which uses a lower-frequency transmit to create a known harmonic acoustical source in tissue suitable for wavefront correction without a priori assumptions of the target or requiring a transponder. The measurement and imaging steps of this method were implemented on the Duke phased array system with a two-dimensional (2-D) array. The method was tested with multiple electronic aberrators [0.39π to 1.16π radians root-mean-square (rms) at 4.17 MHz] and with a physical aberrator 0.17π radians rms at 4.17 MHz) in a variety of imaging situations. Corrections were quantified in terms of peak beam amplitude compared to the unaberrated case, with restoration between 0.6 and 36.6 dB of peak amplitude with a single correction. Standard phantom images before and after correction were obtained and showed both visible improvement and 14 dB contrast improvement after correction. This method, when combined with previous phase correction methods, may be an important step that leads to improved clinical images. PMID:21303031

  18. Mechanistic modeling of aberrant energy metabolism in human disease

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    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  19. Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

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    Jakab, Z; Balogh, E; Kiss, C; Pajor, L; Oláh, E

    1999-01-01

    Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

  20. Prompt cytomolecular identification of chromosome aberration in irradiated blood cells

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    Seyed Akbar Moosavi

    2017-02-01

    Full Text Available Background: understanding the genomic alteration induced by ionizing radiation still remains to be a methodological challenge in genetic field. The energy released from this type of radiation can potentially causes structural and numerical alterations in lymphocytes, which in turn converts them into abnormal tumor cells. Chromosomal abnormalities associated with specific type of hematological malignancies are determinant factors in evaluation of radiation dose and its potential in harming the body. None the less early detection of chromosomal aberration (CA is crucial in prognosis and selection of therapy for the people exposed to irradiations. The aim of this study was to explore a swift and accurate genetic test that identifies CAs in radiologist exposed to X-rays. In addition synergistic effect of other clastogens in irradiated workers was also evaluated. Material and methods: thirty four heparinized blood samples were obtained from radiology workers exposed to X-rays. Blood samples were cultured in RPMI 1640 and F-10 Medias with and without PHA stimulation. Lymphocytes were harvested, separated and arrested at metaphase and their chromosomes were analyzed by solid and G-Banding techniques. Lymphocytic CA was also analyzed through whole chromosome painting FISH. Results: of the 37 blood sample from workers, 60% had various structural aberrations in which both the frequency and type of CAs were intensified among tobacco smokers. Conclusion: the results did not show any significant differences between the genders but other carcinogen like smoking can significantly increases the rate of CAs