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Sample records for aberrant crypt foci

  1. Aberrant crypt foci as microscopic precursors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Lei Cheng; Mao-De Lai

    2003-01-01

    Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), β-catenin, placental cadherin (P-cadherin),epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF Two hypotheses have been proposed.One is the "dysplasia ACF-adenoma-carcinoma sequence",the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dyspiastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo' ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC,and developing preventive procedures.

  2. Correspondence between flat aberrant crypt foci and mucin-depleted foci in rodent colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Paulsen, Jan Erik; Dolara, Piero; Alexander, Jan; Caderni, Giovanna

    2008-01-01

    Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) are preneoplastic lesions identified in the colon of carcinogen-treated rodents stained with methylene blue (MB) and high iron diamine-alcian blue (HID-AB), respectively. The correspondence between flat ACF and MDF in the same colon of Min mice treated with azoxymethane (AOM) and of F344 rats treated with 1,2-dimethylhydrazine (DMH) was explored. The position of each flat ACF was recorded on a digitally constructed photographic map of the MB-stained colon. The same colons were then stained with HID-AB and the position of each MDF was compared with that of flat ACF. The fraction of coincident lesions, identified as both flat ACF and MDF with the two staining methods, was 57% and 42%, in the Min mice and F344 rats, respectively. Flat ACF or MDF not coincident with the two staining methods were either undetectable or ACF with one of the two methods. Flat ACF and MDF show considerable, but not total, overlap.

  3. Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer

    OpenAIRE

    Jay Morris; Michael J. Wargovich; Brown, Vondina R.

    2010-01-01

    Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review, we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on...

  4. 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...... azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCI) (20 mg/kg body weight), respectively, one dose a week for two weeks, Animals were killed after four and 10 weeks, After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci, A much higher number...

  5. Aberrant crypt foci in the colo-rectal mucosa as reliable markers of tumor development

    DEFF Research Database (Denmark)

    Thorup, Inger

    The aim of the present thesis has been to evaluate a recently developed short term in vivo model, the aberrant crypt foci bioassay (ACF), for its ability to predict the development of colo-rectal tumors. Based on the knowledge obtained during the last decade, it can be stated that no simple...... connection exists between occurrence of ACF (neither qualitatively nor quantita- tively) and later development of tumors. However, the literature has shown that part of the ACF show morphologic and genetic features characteristic for the tumorigenic process and a recent investigation indicate that all ACF...... belong to the same unity with basically the same chances for gradual progressing into tumors. It may be speculated that the progression depends on promo- tional conditions in the environment....

  6. Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Schoterman, H.C.; Bruijntjes, J.P.; Hollanders, V.M.H.; Woutersen, R.A.

    2001-01-01

    The aim of the present study was to investigate the effects of galacto-oligosaccharides (GOS, Elix'or) on the development of aberrant crypt foci (ACF) and colorectal tumours in rats treated with azoxymethane (AOM). Two groups of 102 male Fischer 344 rats were injected twice with AOM to induce colore

  7. Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Erk, van M.J.; Doornbos, R.P.; Krul, C.A.M.; Woutersen, R.A.

    2004-01-01

    The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2%

  8. Fluorescence-based SMC and OCT endoscope to study aberrant crypt foci in the mouse colon

    Science.gov (United States)

    Keenan, Molly; Leung, Sarah; Rice, Faith; Wall, R. Andrew; Barton, Jennifer K.

    2013-03-01

    The accepted model of colorectal cancer assumes the paradigm that aberrant crypt foci (ACF) are the earliest events in tumorigenesis and develop into adenoma, which further develop into adenocarcinoma. Under this assumption, basic research and drug studies have been performed using ACF as substitute markers for fully developed carcinoma. While studies have shown a correlation between the number of ACF present and the presence of adenoma/adenocarcinoma, a causal relationship has yet to be determined. The mouse has shown to be an excellent model for colorectal cancer; however, the outcomes of such experiments require sacrifice and histologic examination of ex vivo tissue. To better utilize the mouse model to study ACF and adenoma development, an endoscope was constructed for non-destructive in vivo surface visualization, molecular imaging and cross-sectional imaging of the colon. Our system combines surface magnifying chromoendoscopy (SMC) and optical coherence tomography (OCT) to image colon microstructure. Sixteen mice, treated with the carcinogen azoxymethane, were imaged at 2 week intervals, to visualize carcinogenesis events. With this dual-modality system we are able to visualize crypt structure alteration over time as well as adenoma development over time.

  9. 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.

  10. Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

    Science.gov (United States)

    Hong, Mee Young; Nulton, Emily; Shelechi, Mahshid; Hernández, Lisa M; Nemoseck, Tricia

    2013-01-01

    Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.

  11. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  12. 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.......05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence....... However, the difference is based on few tumors and is not statistically significant. Our results do not show that the number of ACF and crypt multiplicity are conclusively predictive for tumor outcome with the present protocol, which did not include parameters to differentiate between ACF at the cellular...

  13. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.

    Science.gov (United States)

    Bose, A; Elyagoby, A; Wong, T W

    2014-07-01

    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

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

    Science.gov (United States)

    TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATSDavid R. Geter', Tanya M. Moore', Michael H. George', Steve R. Kilburn', Gloria Huggins-Clark', James W. Allen', and Anthony B. DeAngelo' 'National H...

  15. 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 r

  16. Dark Aberrant Crypt Foci with activated Wnt pathway are related to tumorigenesis in the colon of AOM-treated rat

    Directory of Open Access Journals (Sweden)

    Lin Chen

    2008-08-01

    Full Text Available Abstract Background To evaluate the relationship between Aberrant Crypt Foci (ACF and tumorigenesis, we observed the sequential development from ACF to tumor in the colon of azoxymethane-exposed wistar rats. Methods Sixty wistar rats were sacrificed at different time points after exposure to azoxymethane and the colons were stained with methylene blue for stereomicroscopic analysis. Results We found two types of early lesions: classic ACF and dark ACF. Dark ACF were characterized by dark blue staining, mildly enlarged or small compressed crypts that are not elevated from the surrounding epithelium. Large dark ACF and nascent tumors displayed the same surface morphology. Furthermore, dark ACF grew significantly faster than classic ACF and showed dysplasia without hyperplasia. In contrast, classic ACF showed hyperplasia without dysplasia. Dark ACF has significant higher expression rate of β-catenin (100% and MMP-7 (81.82% compared with the expression of β-catenin and MMP-7 in classic ACF (4.84% and 7.87%, respectively. Conclusion Our data indicated that dark ACF is closely related to tumorigenesis while classic ACF is not. Furthermore, Wnt signal pathway was activated during the early period of dark ACF.

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

    Science.gov (United States)

    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.

  18. Efficacy of garbanzo and soybean flour in suppression of aberrant crypt foci in the colons of CF-1 mice.

    Science.gov (United States)

    Murillo, Genoveva; Choi, Juliana K; Pan, Olivia; Constantinou, Andreas I; Mehta, Rajendra G

    2004-01-01

    Epidemiological studies have reported a low incidence of colon cancer in countries with high legume consumption. Moreover, experimental studies have found that legumes, such as soybeans and pinto beans, have anticancer properties. While garbanzo beans are a rich source of various phytochemicals, they have not been well studied. In the present study, the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in CF-1 mice was utilized as a model to assess and compare the effects of garbanzo flour to that of soy flour. Twenty, 5-week-old CF-1 mice were divided into four groups of 5 animals each: 10% garbanzo, 10% soy, 10% mixed (soy and garbanzo flours), and control (rodent chow). Animals received subcutaneous injections of AOM (10-mg/kg B. W.) once a week for two weeks to induce ACF. At week ten, the animals were sacrificed and the colons were scored. There was a 64% (p garbanzo flour, versus an inhibition of 58 and 55% (pgarbanzo beans possess bioactive compounds capable of inhibiting the formation of pre-cancerous lesions in mice and suggest that, like soybeans, their consumption contributes to a reduction in colon cancer incidence.

  19. Beef tallow increases apoptosis and decreases aberrant crypt foci formation relative to soybean oil in rat colon.

    Science.gov (United States)

    Khil, Jinmo; Gallaher, Daniel D

    2004-01-01

    Although epidemiological studies have implicated red meat as increasing colon cancer risk, animal studies have generally not been supportive of such an effect. This study examined red meat components, such as beef protein and tallow, on markers of colon cancer risk. Rats administered dimethylhydrazine were fed either casein or beef protein as the protein source and soybean oil or tallow as the fat source in a 2 2 factorial design for 9 wk. There were fewer preneoplastic lesions [aberrant crypt foci (ACF)] and a greater apoptotic labeling index (P tallow compared with soybean oil. Fecal bile acid concentrations were significantly lower in rats fed tallow compared with soybean oil. There were no significant differences in mucosal cell proliferation. No significant effects were found due to protein source or to interactions between fat and protein sources for ACF, cell proliferation labeling indexes, or bile acid concentrations. However, there was a significant protein by fat source interaction for the apoptotic labeling index. The decreased number of ACF, decreased fecal bile acid concentration, and increased mucosal apoptosis with tallow consumption are not consistent with a role for this fat in increasing risk of colon cancer.

  20. Chemopreventive Potential of Synergy1 and Soybean in Reducing Azoxymethane-Induced Aberrant Crypt Foci in Fisher 344 Male Rats

    Directory of Open Access Journals (Sweden)

    V. P. Gourineni

    2011-01-01

    Full Text Available Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1. Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM- induced aberrant crypt foci (ACF in Fisher 344 male rats. Rats (54 were randomly assigned to 9 groups (n=6. Control group (C was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO2 asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (% in total ACF among treatment groups fed combinations were higher (67–77 compared to groups fed singly (52–64. Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development.

  1. Eicosapentaenoic acid (EPA efficacy for colorectal aberrant crypt foci (ACF: a double-blind randomized controlled trial

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    Higurashi Takuma

    2012-09-01

    Full Text Available Abstract Background Colorectal cancer (CRC is one of the most commonly occurring neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Eicosapentaenoic acid (EPA, the omega-3 polyunsaturated fatty acid that is widely used in the treatment of hyperlipidemia and prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. In CRC chemoprevention trials, in general, the incidence of polyps or of the cancer itself is set as the study endpoint. Although the incidence rate of CRC would be the most reliable endpoint, use of this endpoint would be unsuitable for chemoprevention trials, because of the relatively low occurrence rate of CRC in the general population and the long-term observation period that it would necessitate. Moreover, there is an ethical problem in conducting long-term trials to determine whether a test drug might be effective or harmful. Aberrant crypt foci (ACF, defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are considered as a reliable surrogate biomarker of CRC. Thus, we devised a prospective randomized controlled trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of EPA against colorectal ACF formation and the safety of this drug, in patients scheduled for polypectomy. Methods This study is a multicenter, double-blind, placebo-controlled, randomized controlled trial to be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients shall be recruited for the study and the number of ACF in the rectum counted at the baseline colonoscopy. Then, the participants shall be allocated randomly to either one of two groups, the EPA group and the placebo group. Patients in the EPA group shall receive oral

  2. 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

  3. 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...... 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...

  4. 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

    -type fructan on 1,2-dimethylhydrazine dihydrochloride-induced aberrant crypt foci (ACF) in the rat colon. In addition, the present study investigated the influence of chain length, dietary level (5% or 15%), and duration of feeding (5 or 10 wk) on the following intestinal parameters supposed to be involved......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...

  5. 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.

  6. 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...

  7. 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....

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

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    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.

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

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    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.

  10. A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum.

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    Gillen, Daniel L; Meyskens, Frank L; Morgan, Timothy R; Zell, Jason A; Carroll, Robert; Benya, Richard; Chen, Wen-Pin; Mo, Allen; Tucker, Chris; Bhattacharya, Asmita; Huang, Zhiliang; Arcilla, Myra; Wong, Vanessa; Chung, Jinah; Gonzalez, Rachel; Rodriguez, Luz Maria; Szabo, Eva; Rosenberg, Daniel W; Lipkin, Steven M

    2015-03-01

    Colorectal cancer progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal growth factor receptor (EGFR) inhibitors are efficacious in advanced tumors including colorectal cancer. There is significant evidence that EGFR also plays important roles in colorectal cancer initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and normal rectal tissue. A total of 45 patients were randomized to one of three erlotinib doses (25, 50, and 100 mg) with randomization stratified by nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional prescreening stratification or potentially longer duration of use.

  11. Antioxidant and Anti-inflammatory Effects of Yam (Dioscorea batatas Decne.) on Azoxymethane-induced Colonic Aberrant Crypt Foci in F344 Rats.

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    Son, In Suk; Lee, Jeong Soon; Lee, Ju Yeon; Kwon, Chong Suk

    2014-06-01

    Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental folk medicine because of its nutritional fortification, tonic, anti-diarrheal, anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species (ROS), which are known to be implicated in a range of diseases, may be important progenitors of carcinogenesis. The aim of this study was to investigate the modulatory effect of yam on antioxidant status and inflammatory conditions during azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme activities, colonic mucosal antioxidant enzyme gene expression, and colonic mucosal inflammatory mediator gene expression. The feeding of yam prior to carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam-administered rats, erythrocyte levels of glutathione, glutathione peroxidase (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet. These results suggest that yam could be very useful for the prevention of colon cancer, as they enhance the antioxidant defense system and modulate inflammatory mediators.

  12. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats.

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    Patlolla, Jagan M R; Zhang, Yuting; Li, Qian; Steele, Vernon E; Rao, Chinthalapally V

    2012-01-01

    Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis induction in human colon cancer cells. Five-week-old male F344 rats were fed a control or experimental diet containing two doses of omeprazole (200 and 400 ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for two weeks). Rats continued on experimental diets for seven more weeks before being sacrificed. Colons were histopathologically evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated for different markers associated with proliferation and apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly suppressed total colonic ACF formation (~30%, Pcancer cell lines HCT-116 and HCA-7 cells resulted in induction of p21waf1/cip1 and decreased the expression of anti-apoptotic proteins Bcl-2, Bcl-XL and survivin in a dose-dependent manner. Anticancer properties observed in colon cancer cell lines suggest that omeprazole may induce key signaling molecules of antiproliferation and inhibition of anti-apoptotic proteins.

  13. Suppressive effect of pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay mice.

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    Ueno, Toshiya; Teraoka, Naoya; Takasu, Shinji; Nakano, Katsuya; Takahashi, Mami; Yamamoto, Masafumi; Fujii, Gen; Komiya, Masami; Yanaka, Akinori; Wakabayashi, Keiji; Mutoh, Michihiro

    2012-01-01

    Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator- activated receptor γ(PPARγ) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-Ay obesity and diabetes model mice, and tried to clarify mechanisms by which the PPARγ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF / mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-Ay mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

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

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

    2016-01-01

    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. PMID:27490566

  15. 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.

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

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    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.

  17. Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15-hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis-associated cancer.

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    Kangwan, Napapan; Kim, Yoon-Jae; Han, Young-Min; Jeong, Migyeong; Park, Jong-Min; Hahm, Ki-Baik

    2016-03-15

    The sonic hedgehog (Shh) signaling has been known to contribute to carcinogenesis in organ, where hedgehog exerted organogenesis and in cancers, which are developed based on mutagenic inflammation. Therefore, colitis-associated cancer (CAC) can be a good model to prove whether Shh inhibitors can be applied to prevent, as the efforts to discover potent anti-inflammatory agent are active to prevent CAC. Here, under the hypothesis that Shh inhibitors can prevent CAC, mouse model was generated to develop CAC by azoxymethane (AOM)-initiated, dextran sodium sulfate-promoted carcinogenesis. Shh inhibitors, cerulenin and itraconazole were treated by oral gavage and the mice were sacrificed at early phase of 3 weeks and late phase of 16 weeks. Compared to control group, the number of aberrant crypt foci at 3 weeks and tumor incidence at 16 weeks were all significantly decreased with Shh inhibitor. Significant attenuations of macrophage infiltration accompanied with significant decreases of IL-6, COX-2, STAT3 and NF-κB as well as significant ameliorations of β-catenin nuclear translocation, cyclin D1 and CDK4 were imposed with Shh inhibitors. Especially, CAC was accompanied with significant cancellation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), but their levels were significantly preserved with Shh inhibitors. Among inflammatory mediators, significantly decreased levels of IL-6 and TNF-α, regulated with repressed NF-κb and STAT3, were prominent with Shh inhibitor, whereas significant inductions of apoptosis were noted with Shh inhibitors. In conclusion, Shh inhibitors significantly prevented CAC covering either ameliorating oncogenic inflammation or suppressing tumor proliferation, especially supported with significant inhibition of IL-6 and STAT3 signaling, 15-PGDH preservation and apoptosis induction.

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

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    Saki, Elnaz; Saiful Yazan, Latifah; Mohd Ali, Razana; Ahmad, Zalinah

    2017-01-01

    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.

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

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    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.

  20. Fish Oil Contaminated with Persistent Organic Pollutants Induces Colonic Aberrant Crypt Foci Formation and Reduces Antioxidant Enzyme Gene Expression in Rats.

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    Hong, Mee Young; Hoh, Eunha; Kang, Brian; DeHamer, Rebecca; Kim, Jin Young; Lumibao, Jan

    2017-08-01

    Background: Epidemiologic, clinical, and experimental studies have suggested that fish oil (FO), a rich source of n-3 (ω-3) polyunsaturated fatty acids, protects against colon cancer. However, this message is confounded by the FDA's warning that the consumption of certain types of fish should be restricted because of contamination with persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and organochlorine pesticides.Objective: We examined FO contaminated with POPs (PCBs, dichlorodiphenyltrichloroethane, and chlordane) compared with unmodified FO on the risk factors of colon cancer development.Methods: Male Sprague-Dawley rats aged 28 d (n = 30) were allocated into 3 groups and fed 15% corn oil (CO), FO, or POP-contaminated FO for 9 wk with a subcutaneous injection of colon carcinogen azoxymethane at weeks 3 and 4. Colonic aberrant crypt foci (ACF) and cell proliferation were enumerated, and the gene expression of inflammation, antioxidant enzymes, and repair enzymes were determined with the use of real-time quantitative polymerase chain reaction analysis.Results: FO-fed rats had a lower number of ACF (mean ± SE: 29 ± 4.0 for FO compared with 53 ± 8.4 for CO and 44 ± 4.6 for POP FO) and higher-multiplicity ACF than the CO and POP FO groups (4.7 ± 0.9 for FO compared with 11 ± 1.5 for CO and 9.6 ± 1.8 for POP FO) (P < 0.05). FO feeding lowered the proliferation index compared with the CO and POP FO feeding groups (18% ± 1.1% for FO compared with 25% ± 1.6% for CO and 23% ± 0.7% for POP FO) (P = 0.009). Superoxide dismutase [2.4 ± 0.6 relative quantification (RQ) for FO compared with 1.2 ± 0.2 RQ for CO and 1.3 ± 0.3 RQ for POP FO] and catalase gene expression (10 ± 2.0 RQ for FO compared with 5.4 ± 1.1 RQ for CO and 6.6 ± 1.5 RQ for POP FO) were higher in the FO group than in the CO and POP FO groups (P < 0.05). There were no differences between CO and POP FO on the variables.Conclusion: These results indicate that POPs in

  1. 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

  2. Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats.

    Science.gov (United States)

    Xiao, Rijin; Carter, Julie A; Linz, Amanda L; Ferguson, Matthew; Badger, Thomas M; Simmen, Frank A

    2006-09-01

    We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague-Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis.

  3. Germinated brown rice (GBR) reduces the incidence of aberrant crypt foci with the involvement of beta-catenin and COX-2 in azoxymethane-induced colon cancer in rats.

    Science.gov (United States)

    Latifah, Saiful Yazan; Armania, Nurdin; Tze, Tan Hern; Azhar, Yaacob; Nordiana, Abdul Hadi; Norazalina, Saad; Hairuszah, Ithnin; Saidi, Moin; Maznah, Ismail

    2010-03-26

    Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of beta-catenin and COX-2 reduced significantly (p cancer.

  4. Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4-Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in Azoxymethane-Induced Colorectal Cancer in Rats.

    Science.gov (United States)

    Hajrezaie, Maryam; Shams, Keivan; Moghadamtousi, Soheil Zorofchian; Karimian, Hamed; Hassandarvish, Pouya; Emtyazjoo, Mozhgan; Zahedifard, Maryam; Majid, Nazia Abdul; Mohd Ali, Hapipah; Abdulla, Mahmood Ameen

    2015-07-23

    Schiff-based complexes as a source of cancer chemotherapeutic compounds have been subjected to the variety of anticancer studies. The in-vitro analysis confirmed the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction properties in colon cancer cells, so lead to investigate the inhibitory efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of adult male rats were used in this study: Vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of complex for 10 weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for 2 weeks and orally administered with 5% Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with 15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month. Administration of the complex suppressed total colonic ACF formation up to 73.4% (P < 0.05). The results also showed that treatment with the complex significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining.

  5. Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation: possible role of miR-126/VCAM-1 and miR-126/PI3K/AKT/mTOR.

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    Banerjee, Nivedita; Kim, Hyemee; Talcott, Stephen; Mertens-Talcott, Susanne

    2013-12-01

    The antitumorigenic activities of polyphenols such as ellagitannins and anthocyanins in pomegranate (Punica granatum L.) have been previously studied where cytotoxic, anti-inflammatory and antioxidant effects were evident in various cancer models. The objective of this study was to investigate the role of miR-126/vascular cell adhesion molecule 1 (VCAM-1) and miR-126/phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) in pomegranate-mediated anti-inflammatory and anticarcinogenic effects in vivo and in vitro. Sprague-Dawley rats (n = 10 per group) received pomegranate juice (2504.74 mg gallic acid equivalents/l) or a polyphenol-free control beverage ad libitum for 10 weeks and were injected with azoxymethane (AOM) subcutaneously (15mg/kg) at weeks 2 and 3. Consumption of pomegranate juice suppressed the number of aberrant crypt foci (ACF) and dysplastic ACF by 29 and 53.5% (P = 0.05 and 0.04), respectively, and significantly lowered proliferation of mucosa cells. Pomegranate juice significantly downregulated proinflammatory enzymes nitric oxide synthase and cyclooxygenase-2 messenger RNA (mRNA) and protein expression. In addition, it suppressed nuclear factor-κB and VCAM-1 mRNA and protein expression in AOM-treated rats. Pomegranate also inhibited phosphorylation of PI3K/AKT and mTOR expression and increased the expression of miR-126. The specific target and functions of miR-126 were investigated in HT-29 colon cancer cell lines. In vitro, the involvement of miR-126 was confirmed using the antagomiR for miR-126, where pomegranate reversed the effects of the antagomiR on the expression of miR-126, VCAM-1 and PI3K p85β. In summary, therapeutic potentials of pomegranate in colon tumorigenesis were due in part to targeting miR-126-regulated pathways, which contributes in the underlying anti-inflammatory mechanisms.

  6. 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

  7. 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.

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    Soheil Zorofchian Moghadamtousi

    Full Text Available 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

  8. Mutations of APC and K-ras gene in aberrant crypt foci from human colon%结直肠粘膜隐窝异常病灶K-ras、APC基因突变的研究

    Institute of Scientific and Technical Information of China (English)

    袁平; 张锦生; 孙孟红; 朱雄增; 施达仁

    2001-01-01

    目的 分析隐窝异常病灶(aberrant crypt foci,ACF)的基因水平变化特点及其作为结直肠癌最早期形态变化的分子依据,探讨ACF与腺瘤之间的关系。方法 经微解剖分离提取15例正常粘膜腺体、34例ACF、15例腺瘤和35例结直肠癌组织进行DNA测序,检测K-ras第12、13、61密码子和APC第15外显子“突变密集区”的突变。结果 正常粘膜无K-ras和APC基因突变,ACF、腺瘤和癌组织K-ras突变率分别为17.6%(6/34)、13.3%(2/15)和14.3%(5/35),3者突变率相近。4例ACF、腺瘤和癌组织的突变位于12密码子的第2碱基(GGT→GAT),2例ACF突变发生在13密码子的第2碱基(GGC→GAC)。ACF中K-ras的突变特点与同来源的癌组织保持一致,即患者年龄较大,大体以隆起型为主,所有组织未发现有61密码子的突变。癌和腺瘤APC基因突变率相近,癌为22.9%(8/35),腺瘤为26.7%(4/15)明显高于ACF的2.9%(1/34,P<0.05),癌组织APC与患者的年龄、肿瘤位置、大体类型、组织分化程度无关。结论 ACF可能是结直肠癌最早期的形态改变,ACF的形态学变化、部分基因的改变均有别于腺瘤,提示:(1)ACF有可能是腺瘤前的形态改变;(2) 结直肠癌的发生可能存在“正常上皮→ACF→癌变”这一途径。%Objective To analyze the mutations of K-ras and APC gene in normal colorectal mucosa, aberrant crypt foci (ACF), adenoma and colorectal carcinoma(CRC); To study the genetic alteration in ACF and its possibility of being a molecular marker of very early colon cancer and to explore the relationship of ACF and colorectal adenoma. Methods DNA from 35 CRC, 15 adenomas, 34 ACF and 15 cases of normal mucosa with mucous glands were isolated by micro-dissection. Direct gene sequencing of k-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene. Results Mutation frequency of

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

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    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.

  10. Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model.

    Science.gov (United States)

    Singletary, K W; Meline, B

    2001-01-01

    Cancers of the colon and breast are two of the most prevalent cancers in developed countries. The present experiments were conducted to determine the influence of several dietary doses of grape seed proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis and azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a dual-organ tumor model. In addition, the effects of the grape seed proanthocyanidins on liver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities and on colonic ornithine decarboxylase activity were examined to determine possible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhibition of AOM-induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feeding the grape proanthocyanidins resulted in no significant effect on the activity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. This lack of action on mammary tumorigenesis in part may be due to lack of effect of dietary proanthocyanidins on the liver carcinogen-metabolizing enzymes cytochrome P-450 1A and glutathione S-transferase. These results indicate that grape polyphenolics warrant further evaluation as potential colon cancer chemopreventive agents.

  11. 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.

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

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    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.

  13. Evaluation of Blueberry Juice in Mouse Azoxymethane-Induced Aberrant Crypts and Oxidative Damage

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    Isela Álvarez-González

    2014-01-01

    Full Text Available Blueberry is a plant with a number of nutritional and biomedical capabilities. In the present study we initially evaluated the capacity of its juice (BJ to inhibit the number of aberrant crypts (AC induced with azoxymethane (AOM in mouse. BJ was administered daily by the oral route to three groups of animals during four weeks (1.6, 4.1, and 15.0 μL/g, respectively, while AOM (10 mg/kg was intraperitoneally injected to the mentioned groups, twice a week, in weeks two and three of the assay. We also included two control groups of mice, one administered distilled water and the other the high dose of BJ. A significant increase of AC was observed in the AOM treated animals, and a mean protection of 75.6% was determined with the two low doses of BJ tested; however, the high dose of the juice administered together with AOM increased the number of crypts more than four times the value observed in animals administered only AOM. Furthermore, we determined the antioxidant potential of BJ with an ex vivo DPPH assay and found a dose-dependent decrease with a mean of 19.5%. We also determined the DNA oxidation/antioxidation by identifying 8-hydroxy-2′-deoxyguanosine adducts and found a mean decrease of 44.3% with the BJ administration with respect to the level induced by AOM. Our results show a complex differential effect of BJ related to the tested doses, opening the need to further evaluate a number of factors so as to determine the possibility of a cocarcinogenic potential.

  14. APC and K-ras gene mutation in aberrant crypt foci of human colon

    Institute of Scientific and Technical Information of China (English)

    Ping Yuan; Meng Hong Sun; Jin Sheng Zhang; Xiong Zeng Zhu; Da Ren Shi

    2001-01-01

    AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges, and to explore the relationshipbetween ACF and colorectal adenoma evencarcinoma.METHODS DNA from 35 CRC, 15 adenomas, 34ACF and 10 normal mucus was isolated by meansof microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well asthe mutation cluster region (MCR) of APC genewas performed.RESULTS K-ras gene mutation frequency inACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/ 15), and 14.3% (5/ 35)respectively, showing no difference ( P > 0.05)in K-fas gene mutation among three pathologicprocedures. The K-ras gene mutation inadenoma, carcinoma and 4 ACF restricted incodon 12 (GGT→GAT), but the other 2 mutationsfrom ACF located in codon 13 (GGC→GAC). K-res gene mutation was found more frequently inolder patients and patients with polypoidcancer. No mutation in codon 61 was found in thethree tissue types. Mutation rate of APO gene inadenoma and carcinoma was 22.9% (8/35) and26.7% (4/ 15), which was higher than ACF(2.9%) (P < 0.05). APC gene mutation incarcinoma was not correlated with age ofpatients, location, size and differentiation oftumor.CONCLUSION ACF might be a very earlymorphological lesion in the tumorogenesis ofcolorectal tumor. The morphological feature andgene mutation status was different in ACF andadenoma. ACF is possibly putative"microadenoma" that might be the precursor ofadenoma. In addition, the development of asubgroup of colorectal carcinomas mightundergo a way of "normal epithelium→ ACF→carcinomas".

  15. Inhibitory Effect of Spirulina maxima on the Azoxymethane-induced Aberrant Colon Crypts and Oxidative Damage in Mice

    Science.gov (United States)

    Álvarez-González, Isela; Islas-Islas, Víctor; Chamorro-Cevallos, Germán; Barrios, Juan Pablo; Paniagua, Norma; Vásquez-Garzón, Verónica R.; Villa-Treviño, Saúl; Osiris-Madrigal-Santillán; Morales-González, José Antonio; Madrigal-Bujaidar, Eduardo

    2015-01-01

    Background: Spirulina maxima (Sm) is a cyanobacterium well known because of its high nutritive value, as well as its anti-inflammatory, anti-hyperlipidemic, antioxidant, and anti-genotoxic activities. Objective: To determine the capacity of Sm to inhibit the induction of aberrant colon crypts (AC), as well as the level of lipid peroxidation and DNA oxidative damage in mice treated with azoxymethane (AOM). Materials and Methods: Sm (100, 400, and 800 mg/kg) was daily administered to animals by the oral route during 4 weeks, while AOM (10 mg/kg) was intraperitoneally injected to mice twice in weeks 2 and 3 of the assay. We also included a control group of mice orally administered with distilled water along the assay, as well as other group orally administered with the high dose of Sm. Results: A significant decrease in the number of AC with the three tested doses of Sm, with a mean protection of 51.6% respect to the damage induced by AOM. Also, with the three doses of the alga, we found a reduction in the level of lipoperoxidation, as well as in regard to the percentage of the DNA adduct 8-hydroxy-2’- deoxyguanosine. Conclusion: Sm possesses anti-precarcinogenic potential in vivo, as well as capacity to reduce the oxidative damage induced by AOM. SUMMARY Azoxymethane (AOM) induced a high number of colon aberrant crypts in mouse. It also increased the level of peroxidation and of DNA oxidation in the same organ.Spirulina maxima significantly reduced the number of AOM-induced colon aberrant crypts in mouse. It also reduced the AOM-induced lipid and DNA oxidation in mouse.The results suggest a chemopreventive potential for the tested algae. PMID:27013804

  16. 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

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    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

  17. 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

    2017-01-01

    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. PMID:28106049

  18. 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

    2010-01-01

    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

  19. Foco de criptas aberrantes e câncer da junção colorretal: análise da presença de lesões precoces microscópicas na periferia do câncer colorretal e correlação com a expressão da β-catenina e Ki-67 Aberrant crypt foci and cancer of the colorectal junction: the correlation between β-catenin/Ki-67 expression and the occurrence of early microscopic secondary lesions surrounding periphery colorectal cancer

    Directory of Open Access Journals (Sweden)

    Daniel Cury Ogata

    2010-04-01

    Full Text Available OBJETIVO: Avaliar a presença de foco de criptas aberrantes (FCA em mucosa macroscopicamente normal, localizada na periferia de um câncer colorretal (CCR e correlacionar a progressão tumoral destes FCA para o CCR, por meio da expressão da β-catenina e o Ki-67. MÉTODOS: Utilizou-se 21 espécimes cirúrgicos contendo adenocarcinoma de junção retossigmóide. Foram coletadas amostras localizadas a 1 e 5 cm proximal e distal ao tumor, quando possível, bem como um fragmento da neoplasia. Os FCA foram selecionados. Subseqüentemente foi realizado estudo imunoistoquímico com os anticorpos β-catenina e o Ki-67. RESULTADOS: A expressão nuclear da β-catenina nos adenocarcinomas, revelou freqüência de 81%. O Ki-67 apresentou a mesma freqüência. Apesar disso o coeficiente Kappa revelou fraca concordância entre estes anticorpos. Foram observados 20 FCA, sendo que 13 destes focos localizavam-se nas proximidades do tumor. Nenhum dos FCA apresentou expressão da β-catenina nuclear, tampouco para o Ki-67. CONCLUSÃO: Nas áreas situadas a 1 cm da neoplasia colorretal, foi observada maior concentração de FCA em relação às áreas situadas a 5 cm do tumor. No entanto, não se observou correlação entre a expressão da β-catenina e ki-67 nos colonócitos das criptas aberrantes das áreas estudadas, com as células neoplásicas do adenocarcinoma.OBJECTIVE: To evaluate the occurrence of aberrant crypt foci (ACF in macroscopic normal mucosa surrounding colorectal cancers (CRC; additionally, analyze tumor progression from ACF to CRC by means of β-catenin and Ki-67 expression. METHODS: Twenty-one surgical specimens showing colorectal junction adenocarcinoma were included. Macroscopic normal mucosa proximal and distal to the primary tumor was sampled at a distance of 1 and 5 cm in both sides. A primary tumor sample was also retrieved. Eventually, ACF's were selected and immunohistochemical analysis of β-catenin and Ki-67 were carried out. RESULTS

  20. 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.

  1. Interactive suppression of aberrant crypt foci induced by azoxymethane in rat colon by phytic acid and green tea.

    Science.gov (United States)

    Challa, A; Rao, D R; Reddy, B S

    1997-10-01

    Several epidemiological studies point to a strong correlation between nutrient composition of the diet and cancer of the colon. Phytic acid, present in grains, has been credited with reducing the risk of cancer of the colon. A number of reports are available indicating the benefits of green tea consumption in reducing the risk of stomach, lung and skin cancer, but little data are available on the effect of green tea in reducing the risk of colon cancer. Also, there are no studies on the combined effect of these compounds on colon tumorigenesis. Thus the primary objective of this investigation was to elucidate the combined effects of green tea and phytic acid on colonic preneoplastic lesions and the Phase II enzyme glutathione S-transferase. Fisher 344 male weanling rats were divided into nine groups of 15 rats each and fed the experimental diet for 13 weeks. Rats received two s.c. injections of azoxymethane in saline at 16 mg/kg body wt at 7 and 8 weeks of age. Rats received three levels (0, 1 and 2%) of phytic acid with three levels (0, 1 and 2%) of green tea within each phytic acid level in a 3 x 3 factorial experiment. Results indicate that while green tea had a marginal effect (P green tea and phytic acid was significant (P green tea and phytic acid.

  2. 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.

  3. 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma

    Science.gov (United States)

    Fournier, Alexandra; McLeer-Florin, Anne; Lefebvre, Christine; Duley, Samuel; Barki, Leila; Ribeyron, Juliana; Kassambara, Alboukadel; Hamaidia, Sieme; Granjon, Aurélie; Gressin, Rémy; Lajmanovich, Alicia; Bonnefoix, Thierry; Chauvelier, Stéphanie; Debernardi, Alexandra; Rousseaux, Sophie; de Fraipont, Florence; Figeac, Martin; Kerckaert, Jean-Pierre; De Vos, John; Usson, Yves; Delaval, Katia; Grichine, Alexei; Vourc'h, Claire; Khochbin, Saadi; Feil, Robert; Leroux, Dominique; Callanan, Mary B

    2010-01-01

    Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours—those targeting 1q12 satellite DNA—can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range ‘pairing’ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms. PMID:20432501

  4. 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

    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)....

  5. 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...

  6. Prebiotics prevent the appearance of aberrant crypt foci (ACF) in the colon of BALB/c mice for increasing the gene expression of p16 protein.

    Science.gov (United States)

    Gomides, Antônio Frederico Freitas; de Paula, Sérgio Oliveira; Gonçalves, Reggiani Vilela; de Oliveira, Leandro Licursi; Ferreira, Célia Lúcia de Luces Fortes; Comastri, Débora Silva; Peluzio, Maria do Carmo Gouveia

    2014-10-01

    Existen estudios que demuestran la eficacia de fibras para reducir la aparición de focos de cripta aberrantes (FCA) en roedores. Objetivo: El objetivo de este estudio consistió en investigar los efectos preventivos de los fructooligosacáridos (FOS) y el prebiótico inulina sobre la aparición de FCA en ratones. Materiales y métodos: Las técnicas empleadas fueron: RT-PCR para evaluar la expresión génica de p16, p21, p54, ciclina D1 y ciclina E en el colon distal; la cuantificación del Número de FCA y la medición de la actividad de la catalasa en el hígado y el colon distal. Los animales fueron divididos en cinco tratamientos (n=8); C-: dieta AIN93M sin fibra + DMH (1.2-dimetilhidrazina); INL: dieta AIN93M con inulina; INLCA: dieta AIN93M con inulina + DMH; FOS: dieta ANIN93M con FOS; FOSCA: dieta AIN93M con FOS + DMH, durante 15 semanas. Resultados: La inulina previno la aparición de FCA en el colon proximal, medio y distal, comparado con el control sin fibras. En el colon medio y distal, FOS también fue efectiva para prevenir la incidencia de FCA. Esta efectividad podría ser atribuida al aumento de la expresión génica de p16 tras el tratamiento con FOS. Ambos prebióticos también disminuyeron la actividad de la catalasa en el colon distal, lo que sugiere un efecto antioxidante. Conclusión: Estos resultados sugieren un efecto antioxidante de los prebióticos que podría atribuirse a un aumento de la expresión génica de p16.

  7. 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. Ai

  8. Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

    Science.gov (United States)

    Welge, Weston A.; Barton, Jennifer K.

    2016-03-01

    Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

  9. Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Sakai, Eiji; Morioka, Takamitsu; Yamada, Eiji; Ohkubo, Hidenori; Higurashi, Takuma; Hosono, Kunihiro; Endo, Hiroki; Takahashi, Hirokazu; Takamatsu, Reika; Cui, Changxu; Shiozawa, Manabu; Akaike, Makoto; Samura, Hironori; Nishimaki, Tadashi; Nakajima, Atsushi; Yoshimi, Naoki

    2012-01-01

    In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis. © 2011 Japanese Cancer Association.

  10. 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

  11. 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...

  12. Histological and immunohistochemical observations of mucin-depleted foci (MDF) stained with Alcian blue, in rat colon carcinogenesis induced with 1,2-dimethylhydrazine dihydrochloride.

    Science.gov (United States)

    Yoshimi, Naoki; Morioka, Takamitsu; Kinjo, Tatsuya; Inamine, Morihiko; Kaneshiro, Tatsuya; Shimizu, Takahiro; Suzui, Masumi; Yamada, Yasuhiro; Mori, Hideki

    2004-10-01

    The usefulness of mucin-depleted foci (MDF), which have recently been proposed as a new preneoplastic biomarker in rat colon carcinogenesis, was histologically investigated in rat colonic tissues treated with 1,2-dimethylhydrazine dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and beta-catenin accumulated crypts (BCAC) was examined by comparing the corresponding computer-captured images. Twelve male F344 rats were given DMH s.c. at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided into two groups. Rats in group 1 were given normal drinking water, while those in group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6 weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The resected colons were fixed in 10% formalin, and stained with Alcian blue for observation of ACF and MDF. Histological and immunohistochemical analysis revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated with IND) were significantly decreased, compared with those in group 1. The number of BCAC in group 2 was also significantly lower than that in group 1. The reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF. Analyses of the computer-captured images indicated that MDF had more frequent dysplastic changes and overexpression of beta-catenin than did ACF. MDF having over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These results suggest that MDF may be useful as an early biomarker in colon carcinogenesis.

  13. Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Dolara, Piero; Caderni, Giovanna

    2004-02-01

    Crypt foci with absent or scant mucous production (mucin-depleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg x 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number of MDF was significantly increased in rats treated with CHA (PMDF/colon were 6.10 +/- 1.26, 10.59 +/- 1.96 and 1.31 +/- 0.21 in controls, CHA and PXC groups, respectively, means +/- SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of 'large' MDF, formed by 12 or more crypts, was also reduced (PMDF were 1.7 +/- 0.5 and 0.4 +/- 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

  14. 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...

  15. Enzootic plague foci, Algeria

    Science.gov (United States)

    Malek, M.A.; Hammani, A.; Beneldjouzi, A.; Bitam, I.

    2014-01-01

    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. PMID:25834736

  16. 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.

  17. Effect of etoricoxib, a cyclooxygenase-2 selective inhibitor on aberrant crypt formation and apoptosis in 1,2 dimethyl hydrazine induced colon carcinogenesis in rat model Efecto del etoricoxib, un inhibidor selectivo de la ciclooxigenasa-2, sobre la formación de criptas aberrantes y la apoptosis en un modelo murino de carcinogénesis de colon inducidad por 1,2-dimetilhidracina

    Directory of Open Access Journals (Sweden)

    P. Sharma

    2010-02-01

    Full Text Available Etoricoxib, a second generation selective cyclooxygenase-2 (COX-2 inhibitor had been studied for the chemopreventive response at its therapeutic anti-inflammatory dose in 1,2-dimethylhydrazine (DMH induced colon carcinogenesis in rat model. Eight to ten weeks old male rats of Sprague-Dawley strain were divided into four groups. While group 1 served as control and received the vehicle of the drugs, group 2 and 3 were administered freshly prepared DMH in 1mM EDTA-saline (pH 7.0 (30 mg/kg body wt/week, subcutaneously. Group 3 was also given a daily treatment of etoricoxib (0.6 mg/kg body wt orally while the group 4 received the same amount of etoricoxib only, prepared in 0.5% carboxymethyl cellulose. Animals were sacrificed at the end of 6 weeks, body weight recorded and the colons were subjected to macroscopic and histopathological studies. The maximum number of raised mucosal lesions called the multiple plaque lesions (MPL were found in the DMH group which significantly reverted back in the DMH + etoricoxib group, while very few MPLs were recorded in the control and etoricoxib only group. Similarly, the number of aberrant crypt foci (ACF, the point of future carcinogenic growth, was recorded more in the DMH group and significantly less in the DMH + etoricoxib group. The histopathological analysis showed the presence of severe hyperplasia, occasional dysplasia and aggregates of lymphoid cells in the localized regions. Etoricoxib group showed near normal histological features with the crypt architecture and the surrounding stromal tissue remaining intact. To ascertain the molecular mechanism of such anti-carcinogenic features the colonocytes were isolated and studied in primary culture for the evidence of apoptosis by fluorescent staining and genotoxic changes by single cell gel electrophoresis assay (comet assay which shows that the DMH treated animals produced much less apoptotic nuclei but more comet producing cell, while these features were

  18. Pre-neoplastic lesion, mucin-depleted foci, reveals de novo high-grade dysplasia in rat colon carcinogenesis.

    Science.gov (United States)

    Cui, Changxu; Takamatsu, Reika; Doguchi, Hiroshi; Matsuzaki, Akiko; Saio, Masanao; Yoshimi, Naoki

    2012-05-01

    Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in tumors, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to those in tumors. The incidence of ACF, which was much higher than that of tumors, also increased gradually in a time-dependent manner. The incidence of MDF, however, was similar to that of tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC features. Even at 5 weeks, MDF showed features of DHG. We classified these into two forms of MDF: flat and protruded MDF. At 40 weeks, the number of flat MDF per colon decreased significantly compared with that at 20 weeks (pMDF per colon increased (pMDF lesion decreased but that of AC increased remarkably. In conclusion, MDF may develop into cancer through the so-called 'de novo cancer' pathway.

  19. Foci of Volcanoes

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, I.

    1974-01-01

    One may assume a center of volcanic activities beneath the edifice of an active volcano, which is here called the focus of the volcano. Sometimes it may be a ''magma reservoir''. Its depth may differ with types of magma and change with time. In this paper, foci of volcanoes are discussed from the viewpoints of four items: (1) Geomagnetic changes related with volcanic activities; (2) Crustal deformations related with volcanic activities; (3) Magma transfer through volcanoes; and (4) Subsurface structure of calderas.

  20. 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

    2010-07-01

    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 x 2 x 2 x 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 < 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized 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 nonpromoting processed meat. 2010 AACR.

  1. Modelling the dynamics of stem cells in colonic crypts

    Science.gov (United States)

    Sirio, Orozco-Fuentes; Barrio, Rafael A.

    2017-02-01

    We present a theoretical and computational framework to model the colonic crypt organisation in the human intestine. We construct a theoretical and computational framework to model the colonic crypt behaviour, using a Voronoi tessellation to represent each cell and elastic forces between them we addressed how their dynamical disfunction can lead to tumour masses and cancer. Our results indicate that for certain parameters the crypt is in a homeostatic state, but slight changes on their values can disrupt this behaviour.

  2. 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.

  3. Patterns of proliferative activity in the colonic crypt determine crypt stability and rates of somatic evolution.

    Directory of Open Access Journals (Sweden)

    Rui Zhao

    Full Text Available Epithelial cells in the colon are arranged in cylindrical structures called crypts in which cellular proliferation and migration are tightly regulated. We hypothesized that the proliferation patterns of cells may determine the stability of crypts as well as the rates of somatic evolution towards colorectal tumorigenesis. Here, we propose a linear process model of colonic epithelial cells that explicitly takes into account the proliferation kinetics of cells as a function of cell position within the crypt. Our results indicate that proliferation kinetics has significant influence on the speed of cell movement, kinetics of mutation propagation, and sensitivity of the system to selective effects of mutated cells. We found that, of all proliferation curves tested, those with mitotic activities concentrated near the stem cell, including the actual proliferation kinetics determined in in vivo labeling experiments, have a greater ability of delaying the rate of mutation accumulation in colonic stem cells compared to hypothetical proliferation curves with mitotic activities focused near the top of the crypt column. Our model can be used to investigate the dynamics of proliferation and mutation accumulation in spatially arranged tissues.

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

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

    Lifescience Database Archive (English)

    Full Text Available His.Dig.10.AllAg.Intestinal_crypt mm9 Histone Digestive tract Intestinal crypt http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Dig.10.AllAg.Intestinal_crypt.bed ...

  10. 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 ...

  11. Crypt region localization of intestinal stem cells in adults

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients, but exists in a harsh luminal environment that necessitates continual renewal. This renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal surface. This process is dependent on multi-potent progenitor cells, or stem cells, located in each crypt. There are about 4 to 6 stem cells per crypt, and these stem cells are believed to generate distinct end-differentiated epithelial cell types, including absorptive cells, goblet cells, enteroendocrine cells and Paneth cells, while also maintaining their own progenitor cell state. Earlier studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [i.e. Crypt base columnar (CBC) cell model] or at an average position of 4 cells from the crypt base [I.e. Label-retaining cells (LRC +4) model]. Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal crypt. Most notable of these novel markers are Lgr5, a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells, and Bmi 1, which encodes a chromatin remodeling protein expressed by LRC. These studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.

  12. 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

  13. Pelvic Gliomatosis within Foci of Endometriosis

    OpenAIRE

    Killeen, Vincent B.; Reich, Harry; McGlynn, Fran; Virgilio, Lawrence A.; Krawitz, Michael A.; Sekel, Lisa

    1997-01-01

    The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.

  14. 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.

  15. Locating Ectopic Foci on a Cylinder

    Science.gov (United States)

    Kuklik, Pawel; Zebrowski, Jan J.

    2003-07-01

    Arrhythmia is a condition in which an additional ectopic pacemaker is present in the tissue of the heart. Localization of ectopic foci is essential for successful radio-frequency ablation, an important surgical way of treating arrhythmia. In one of the possible mechanisms, arrhythmia induced by an ectopic foci located in one of the main blood vessels leading out or onto the heart. The therapeutic procedure in this case is usually ablation of the whole junction of the blood vessel with heart wall. In this way, whatever excitation occurs inside the vessel, it cannot penetrate the ventricles perturbing their contraction cycle. Such an ablation procedure is long and burdened with the risk of the perforation. A more safe method would involve the localization of the source of the excitation (i.e. the ectopic foci) and its ablation. The methods used in cardiology at present involve complicated localization systems and are time-consuming with the patient spending a long time on the operating table. Recently, Hall and Glass have developed numerical methods which allow to quickly to model the localization of the ectopic foci in a flat, square sample of an inhomogeneous medium. Here, we demonstrate an extension of this model for the case of a cylinder containing an ectopic foci, that can be a model of a blood vessel with the source of the ectopic beat inside it. Three methods of localization are implemented. Standard electrodes containing several active tips are used to stimulate the medium locally and locate the foci judging from the reaction of the system. The first one uses electrode activation times to compute the location of the ectopic site. The second one localizes it by measuring the resetting response of the foci, and the third one, uses wavefront curvature. Specifically for the cylindrical geometry of the blood vessel, we developed a localization procedure that allows to quickly localize the pacemaker.

  16. FauxCrypt - A Method of Text Obfuscation

    CERN Document Server

    Gualtieri, Devlin M

    2010-01-01

    Warnings have been raised about the steady diminution of privacy. More and more personal information, such as that contained electronic mail, is moving to cloud computing servers where it might be machine-searched and indexed. FauxCrypt is an algorithm for modification of a plaintext document that leaves it generally readable by a person but not readily searched or indexed by machine. The algorithm employs a dictionary substitution of selected words, and an obfuscating transposition of letters in other words. The obfuscation is designed to leave the words understandable, although they are badly spelled. FauxCrypt is free, open source software, with source code available.

  17. Crypt abscess-associated microbiota in inflammatory bowel disease and acute self-limited colitis

    Institute of Scientific and Technical Information of China (English)

    Harry; Sokol; Nadia; Vasquez; Nadia; Hoyeau-Idrissi; Philippe; Seksik; Laurent; Beaugerie; Anne; Lavergne-Slove; Philippe; Pochart; Philippe; Marteau

    2010-01-01

    AIM:To evaluate whether crypt abscesses frominflammatory bowel disease(IBD)patients containbacteria and to establish their nature.METHODS:We studied 17 ulcerative colitis patients,11 Crohn's disease patients,7 patients with acute selflimited colitis(ASLC)and normal colonic biopsies from5 subjects who underwent colonoscopy for colon cancer screening.A fluorescent in situ hybridization techniquewas applied to colonic biopsies to assess the microbiotacomposition of the crypts and crypt abscesses.RESULTS:Crypts...

  18. File list: DNS.Dig.50.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Dig.50.AllAg.Intestinal_crypt mm9 DNase-seq Digestive tract Intestinal crypt ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Dig.50.AllAg.Intestinal_crypt.bed ...

  19. File list: NoD.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.10.AllAg.Intestinal_crypt mm9 No description Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.10.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.05.AllAg.Intestinal_crypt mm9 RNA polymerase Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.05.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.10.AllAg.Intestinal_crypt mm9 All antigens Digestive tract Intestinal crypt... SRX871676,SRX871671,SRX871675,SRX871672 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Dig.10.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.20.AllAg.Intestinal_crypt mm9 No description Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.20.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.20.AllAg.Intestinal_crypt mm9 RNA polymerase Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.20.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.05.AllAg.Intestinal_crypt mm9 TFs and others Digestive tract Intestinal cry...pt SRX871676,SRX871675,SRX871671,SRX871672 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Dig.05.AllAg.Intestinal_crypt.bed ...

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

    Lifescience Database Archive (English)

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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.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.10.AllAg.Intestinal_crypt mm9 RNA polymerase Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.10.AllAg.Intestinal_crypt.bed ...

  9. File list: InP.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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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: InP.Dig.05.AllAg.Crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Dig.10.AllAg.Crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  19. Chicago aberration correction work.

    Science.gov (United States)

    Beck, V D

    2012-12-01

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system.

  20. Chicago aberration correction work

    Energy Technology Data Exchange (ETDEWEB)

    Beck, V.D., E-mail: vnlbeck@earthlink.net [1 Hobby Drive, Ridgefield, CT 06877-01922 (United States)

    2012-12-15

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system. -- Highlights: Black-Right-Pointing-Pointer Crewe and his group made significant advances in aberration correction and reduction. Black-Right-Pointing-Pointer A deeper understanding of the quadrupole octopole corrector was developed. Black-Right-Pointing-Pointer A scheme to correct spherical aberration using hexapoles was developed. Black-Right-Pointing-Pointer Chromatic aberration was corrected using a uniform field mirror.

  1. Aberration compensation and resolution improvement of focus modulation microscopy

    Science.gov (United States)

    Zheng, Juanjuan; Gao, Peng; Shao, Xiaopeng

    2017-01-01

    Confocal laser scanning microscopy (CLSM) has wide applications in biological research and medical diagnosis. However, the spatial resolution and signal to noise ratio (SNR) of CLSM is reduced in the presence of an aberration. Here we improve the pupil-segmentation method to measure and compensate for aberrations in focus modulation CLSM (FM-CLSM), which uses Gaussian-type and doughnut-like foci to scan a sample in sequence. As a result, FM-CLSM can provide images with a high resolution and a high SNR for biomedical or industrial applications.

  2. Memory based active contour algorithm using pixel-level classified images for colon crypt segmentation.

    Science.gov (United States)

    Cohen, Assaf; Rivlin, Ehud; Shimshoni, Ilan; Sabo, Edmond

    2015-07-01

    In this paper, we introduce a novel method for detection and segmentation of crypts in colon biopsies. Most of the approaches proposed in the literature try to segment the crypts using only the biopsy image without understanding the meaning of each pixel. The proposed method differs in that we segment the crypts using an automatically generated pixel-level classification image of the original biopsy image and handle the artifacts due to the sectioning process and variance in color, shape and size of the crypts. The biopsy image pixels are classified to nuclei, immune system, lumen, cytoplasm, stroma and goblet cells. The crypts are then segmented using a novel active contour approach, where the external force is determined by the semantics of each pixel and the model of the crypt. The active contour is applied for every lumen candidate detected using the pixel-level classification. Finally, a false positive crypt elimination process is performed to remove segmentation errors. This is done by measuring their adherence to the crypt model using the pixel level classification results. The method was tested on 54 biopsy images containing 4944 healthy and 2236 cancerous crypts, resulting in 87% detection of the crypts with 9% of false positive segments (segments that do not represent a crypt). The segmentation accuracy of the true positive segments is 96%.

  3. Actin Foci Adhesion of D. discoideum

    Science.gov (United States)

    Flanders, Bret; Paneru, Govind

    2014-03-01

    Amoeboid migration is a fast (10 μm min-1) integrin-independent mode of migration that is important with D. discoideum, leukocytes, and breast cancer cells. It is poorly understood, but depends on the establishment of adhesive contacts to the substrate where the cell transmits traction forces. In pre-aggregative D. discoideum, a model system for learning about amoeboid migration, these adhesive contacts are discrete complexes that are known as actin-foci. They have an area of ~ 0.5 μm2 and a lifetime of ~ 20 s. This talk will present measurements of the adhesive character of actin foci that have been obtained using a submicron force transducer that was designed for this purpose. Results on the rupture stresses and lifetimes of individual acting foci under nano-newton level forces will be described in the context of a general theory for cellular adhesion. This theory depends on, essentially, three cellular properties: the membrane-medium surface tension, the number density of adhesion receptors in the membrane, and the receptor-substrate potential energy surface. Therefore, the use of the transducer to determine the surface tension will be presented, as well.

  4. A Model of Colonic Crypts using SBML Spatial

    Directory of Open Access Journals (Sweden)

    Carlo Maj

    2013-09-01

    Full Text Available The Spatial Processes package enables an explicit definition of a spatial environment on top of the normal dynamic modeling SBML capabilities. The possibility of an explicit representation of spatial dynamics increases the representation power of SBML. In this work we used those new SBML features to define an extensive model of colonic crypts composed of the main cellular types (from stem cells to fully differentiated cells, alongside their spatial dynamics.

  5. Crypt cells are involved in kin recognition in larval zebrafish

    Science.gov (United States)

    Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F.

    2016-01-01

    Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal. PMID:27087508

  6. 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.

  7. Aberration Corrected Emittance Exchange

    CERN Document Server

    Nanni, Emilio A

    2015-01-01

    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (RF) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dog-leg emittance exchange setup with a 5 cell RF deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of emittances differing by 4 orders of magnitude, i.e. an initial transverse emittance of $\\epsilon_x=1$ pm-rad is exchanged with a longitudinal emittance of $\\epsilon_z=10$ nm-rad.

  8. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  9. 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

  10. 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

  11. Biosynthesis of intestinal microvillar proteins. Expression of aminopeptidase N along the crypt-villus axis

    DEFF Research Database (Denmark)

    Danielsen, E M

    1984-01-01

    in the crypt cells and a moderate increase of about 20% in the villus cells. Whereas the latter can possibly be ascribed to a general protective effect of dexamethasone on villus architecture, these experiments indicate that crypt cells of mucosa from adult individuals exhibit the same sensitivity...

  12. 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

  13. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.

    NARCIS (Netherlands)

    Es, J.H. van; Gijn, M.E. van; Riccio, O.; Born, M. van den; Vooijs, M.; Begthel, H.; Cozijnsen, M.; Robine, S.; Winston, D.J.; Radtke, F.; Clevers, J.C.

    2005-01-01

    The self-renewing epithelium of the small intestine is ordered into stem/progenitor crypt compartments and differentiated villus compartments. Recent evidence indicates that the Wnt cascade is the dominant force in controlling cell fate along the crypt-villus axis. Here we show a rapid, massive

  14. 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 permanen

  15. 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

  16. Analysis of cryptographic mechanisms used in ransomware CryptXXX v3

    Directory of Open Access Journals (Sweden)

    Michał Glet

    2016-12-01

    Full Text Available The main purpose of this paper was to analysis how malicious software is using cryptographic mechanisms. Reverse engineering were applied in order to discover mechanisms used in ransomware CryptXXX v3. At the end were given some useful advices how to improve CryptXXX.[b]Keyword:[/b] ransomware, software engineering, reverse engineering, RC4, RSA, malicious software

  17. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.

    NARCIS (Netherlands)

    Es, J.H. van; Gijn, M.E. van; Riccio, O.; Born, M. van den; Vooijs, M.; Begthel, H.; Cozijnsen, M.; Robine, S.; Winston, D.J.; Radtke, F.; Clevers, J.C.

    2005-01-01

    The self-renewing epithelium of the small intestine is ordered into stem/progenitor crypt compartments and differentiated villus compartments. Recent evidence indicates that the Wnt cascade is the dominant force in controlling cell fate along the crypt-villus axis. Here we show a rapid, massive conv

  18. 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, go

  19. Analysis of cryptographic mechanisms used in ransomware CryptXXX v3

    OpenAIRE

    Michał Glet

    2016-01-01

    The main purpose of this paper was to analysis how malicious software is using cryptographic mechanisms. Reverse engineering were applied in order to discover mechanisms used in ransomware CryptXXX v3. At the end were given some useful advices how to improve CryptXXX.[b]Keyword:[/b] ransomware, software engineering, reverse engineering, RC4, RSA, malicious software

  20. 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

    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......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...... changes associated with colon inflammation such as a decline in crypt numbers and an increase in crypts width throughout the large intestine. Thus it appears that AOM lower the threshold level for inflammation-induced changes which potentially may lead to neoplasia....

  1. 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

  2. Stem cell self-renewal in intestinal crypt

    Energy Technology Data Exchange (ETDEWEB)

    Simons, Benjamin D., E-mail: bds10@cam.ac.uk [Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE (United Kingdom); The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN (United Kingdom); Clevers, Hans, E-mail: h.clevers@hubrecht.eu [Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht (Netherlands)

    2011-11-15

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine and colon has remained the subject of debate. Recent studies based on targeted lineage tracing strategies, combined with the development of an organotypic culture system, have identified the crypt base columnar cell as the intestinal stem cell, and have unveiled the strategy by which the balance between proliferation and differentiation is maintained. These results show that intestinal stem cells operate in a dynamic environment in which frequent and stochastic stem cell loss is compensated by the proliferation of neighboring stem cells. We review the basis of these experimental findings and the insights they offer into the mechanisms of homeostatic stem cell regulation.

  3. 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.

  4. 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

  5. Multiple coaxial foci generation by phase-only pupil filters

    Science.gov (United States)

    Valle, Pedro J.; Oti, José E.; Canales, Vidal F.; Cagigal, Manuel P.

    2007-04-01

    A new procedure for creating simultaneous multiple foci along the same optical axis with phase-only pupil-plane filters is proposed. Pupil-plane filters consist in phase-only masks described by simple circularly symmetric analytical functions. The axial separation between foci and their energy distribution are independently controlled by two different parameters of the filter. The main advantage of this new design is that, unlike other methods that required slow iterative algorithms, the proposed phase masks are straightforwardly calculated from analytical expressions. Moreover, real-time dynamic foci control could be achieved by using a computer addressed spatial light modulator that allowed the generation of variable phase patterns. The phase profiles we propose can be combined with multiple transversal foci phase patterns to actually form axial replicas of the transversal foci. Thus, it should be expected that three-dimensional structures were dynamically driven fast enough to perform real-time interactive multiple foci manipulation. Experimental verification of the multiple coaxial foci creation by static phase filters is shown.

  6. Fluorescent foci quantitation for high-throughput analysis

    Science.gov (United States)

    Ledesma-Fernández, Elena; Thorpe, Peter H.

    2015-01-01

    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. PMID:26290880

  7. 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.

  8. Cell Organisation in the Colonic Crypt: A Theoretical Comparison of the Pedigree and Niche Concepts

    Science.gov (United States)

    van der Wath, Richard C.; Gardiner, Bruce S.; Burgess, Antony W.; Smith, David W.

    2013-01-01

    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. PMID:24069177

  9. Mapping risk foci for endemic sheep scab.

    Science.gov (United States)

    Rose, H; Learmount, J; Taylor, M; Wall, R

    2009-10-28

    Psoroptic mange in sheep, resulting from infestation by the astigmatid mite Psoroptes ovis, is increasingly prevalent in Europe and other parts of the world. As a step towards improved national control, regional or local scab management programmes that target high-risk areas and aim to maintain the number of outbreaks below an acceptable level may be an effective initial use of time and resource. To facilitate such a management approach, in this paper scab outbreak farms are identified using a questionnaire survey of sheep farmers, the data from which are then used to build a national scab risk model for Great Britain. The questionnaire results indicate a national prevalence of scab, between March 2007 and February 2008, of 8.6% (+/-1.98). However, previous exposure to sheep scab significantly affected the respondent's probability of reporting a scab outbreak during the survey period (chi(2)=53.2, d.f.=1, P<0.001); 85% of the farms that reported at least one scab outbreak had experienced outbreaks in previous years, 27% had experienced outbreaks in more than five of the previous 10 years. In contrast, 76% of farms that did not report scab had not had a previous outbreak. The highest prevalence areas were in Northern England, Wales, Southwest England and Scotland. Modelling the distribution of the reported scab outbreaks identified height above sea level, temperature and rainfall as significant predictors of the probability of an outbreak, superimposed on an underlying pattern of sheep abundance. It is argued that scab management programmes directed at these foci have the potential to allow a more targeted approach to scab control and significantly reduce the prevalence of scab in the UK and other European countries.

  10. Dicentric chromosomes and gamma-H2AX foci formation in lymphocytes of human blood samples exposed to a CT scanner: a direct comparison of dose response relationships.

    Science.gov (United States)

    Golfier, Sven; Jost, Gregor; Pietsch, Hubertus; Lengsfeld, Philipp; Eckardt-Schupp, Friederike; Schmid, Ernst; Voth, Matthias

    2009-02-01

    Experiments using the induction of dicentric chromosomes (dicentrics) as well as the gamma-H2AX foci formation in lymphocytes of blood samples from a healthy donor were performed to directly evaluate the radiation sensitivity of both biological endpoints. For computed tomography scans at dose levels from 0.025 to 1 Gy, a linear-quadratic dose-response relationship for dicentrics and a linear dose-response relationship for gamma-H2AX foci were obtained. The coefficients of the dose-response relationship for dicentrics are alpha = (3.76 +/- 0.29) x 10(-2) Gy(-1) and beta = (5.54 +/- 0.45) x 10(-2) Gy(-2), the linear coefficient for gamma-H2AX foci is (7.38 +/- 0.11) Gy(-1). The findings indicate that scoring of dicentrics as well as microscopic analysis of gamma-H2AX foci are sensitive methods to quantify a radiation-induced biological damage at low doses. However, since gamma-H2AX foci can be partially repaired within a few hours, biological damages present for days or even months, which constitute the clinically relevant endpoints, can only be quantified reliably by scoring of chromosome aberrations. Thus currently the quantification of dicentrics or reciprocal translocations remains the recommended method for estimating the effect of exposures to low dose levels of radiation ('biological dosimetry'). However, owing to the high radiation sensitivity of the gamma-H2AX foci assay observed in the present study, further investigations on the effectiveness of low-linear energy transfer radiation qualities in producing gamma-H2AX foci in lymphocytes from healthy donors should be performed.

  11. Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.

    Science.gov (United States)

    Femia, Angelo Pietro; Swidsinski, Alexander; Dolara, Piero; Salvadori, Maddalena; Amedei, Amedeo; Caderni, Giovanna

    2012-01-01

    Mucin depleted foci (MDF) are precancerous lesions of the colon in carcinogen-treated rodents and humans at high risk. Since MDF show signs of inflammation we hypothesized that the defective mucous production would expose them to the risk of being penetrated by intestinal bacteria, which can be sensed by Toll-like receptors (Tlrs) and activate inflammatory pathways. To verify this hypothesis we tested the expression of 84 genes coding for Tlrs and associated pathways using RT-qPCR in MDF (n = 7) from 1,2-dimethylhydrazine (DMH)-treated rats. Among the 84 tested genes, 26 were differentially expressed in MDF with 5 genes significantly up-regulated and 21 down-regulated when compared to the normal mucosa. Tlr2, as well as other downstream genes (Map4k4, Hspd1, Irak1, Ube2n), was significantly up-regulated. Among the genes regulating the NFkB pathway, only Map4k4 was significantly up-regulated, while 19 genes were not varied and 6 were down-regulated. Tlr2 protein was weakly expressed both in normal mucosa and MDF. To determine whether inflammation observed in MDF could be caused by bacteria contacting or infiltrating crypts, we performed fluorescence in situ hybridization (FISH) experiments with a rRNA universal bacterial probe. None of the 21 MDF tested, showed bacteria inside the crypts, while among the colonic tumors (n = 15), only one had very few bacteria on the surface and on the surrounding normal mucosa. In conclusion, the up-regulation of Tlr2 in MDF, suggests a link between this receptor and carcinogenesis, possibly related to a defective barrier function of these lesions. The data of FISH experiments do not support the hypothesis that inflammation in MDF and tumors is stimulated by bacterial infiltration.

  12. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Directory of Open Access Journals (Sweden)

    Ann-Marie Baker

    2014-08-01

    Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

  13. 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.

  14. A reaction–diffusion mechanism influences cell lineage progression as a basis for formation, regeneration, and stability of intestinal crypts

    Directory of Open Access Journals (Sweden)

    Zhang Lei

    2012-07-01

    Full Text Available Abstract Background Colon crypts, a single sheet of epithelia cells, consist of a periodic pattern of stem cells, transit-amplifying cells, and terminally differentiated cells that constantly renew and turnover. Experimental evidence suggests that Wnt signaling promotes and regulates stem cell division, differentiation, and possible cell migrations while intestinal BMP signaling inhibits stem cell self-renewal and repression in crypt formation. As more molecular details on Wnt and BMP in crypts are being discovered, little is still known about how complex interactions among Wnt, BMP, and different types of cells, and surrounding environments may lead to de novo formation of multiple crypts or how such interactions affect regeneration and stability of crypts. Results We present a mathematical model that contains Wnt and BMP, a cell lineage, and their feedback regulations to study formation, regeneration, and stability of multiple crypts. The computational explorations and linear stability analysis of the model suggest a reaction–diffusion mechanism, which exhibits a short-range activation of Wnt plus a long-range inhibition with modulation of BMP signals in a growing tissue of cell lineage, can account for spontaneous formation of multiple crypts with the spatial and temporal pattern observed in experiments. Through this mechanism, the model can recapitulate some distinctive and important experimental findings such as crypt regeneration and crypt multiplication. BMP is important in maintaining stability of crypts and loss of BMP usually leads to crypt multiplication with a fingering pattern. Conclusions The study provides a mechanism for de novo formation of multiple intestinal crypts and demonstrates a synergetic role of Wnt and BMP in regeneration and stability of intestinal crypts. The proposed model presents a robust framework for studying spatial and temporal dynamics of cell lineages in growing tissues driven by multiple signaling

  15. HIV enteropathy: crypt stem and transit cell hyperproliferation induces villous atrophy in HIV/Microsporidia-infected jejunal mucosa.

    Science.gov (United States)

    Batman, Philip A; Kotler, Donald P; Kapembwa, Moses S; Booth, Dawn; Potten, Christopher S; Orenstein, Jan M; Scally, Andrew J; Griffin, George E

    2007-02-19

    The study aim was to analyse the kinetics of stem and transit cells in the crypts of jejunal mucosa infected with HIV and Microsporidia. The size of villi, depth of crypts and proliferative activity of transit and stem cells in jejunal mucosa were measured using morphometric techniques. The surface area/volume ratio (S/V) of jejunal biopsies was estimated under light microscopy using a Weibel graticule. Crypt length was measured by counting enterocytes along the crypt side from the base to the villus junction, and the mean crypt length was calculated. The S/V and crypt lengths of the jejunal mucosa of 21 HIV and Microsporidia-infected test cases were compared with 14 control cases. The labelling index in relation to the crypt cell position of 10 of the test cases was analysed compared with 13 control cases. Differences were found in the S/V and crypt length, and there was a negative correlation between S/V and crypt length in test and control cases combined. Cell labelling indices fell into low and high proliferation groups. There were significant differences in labelling indices between low proliferation test cases and controls, between high proliferation test cases and controls, and between high and low proliferation test cases. Villous atrophy induced by HIV and Microsporidia is attributed to crypt cell hyperplasia and the encroachment of crypt cells onto villi. These infections induce crypt hypertrophy by stimulating cell mitosis predominantly in transit cells but also in stem cells. Increased stem cell proliferation occurs only in high proliferation cases.

  16. 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.

  17. 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.

  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

    2013-01-01

    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

  19. Three-dimensional array foci of generalized Fibonacci photon sieves

    CERN Document Server

    Zhang, Junyong; Zhu, Jianqiang; Lin, Zunqi

    2015-01-01

    We present a new kind of photon sieves on the basis of the generalized Fibonacci sequences. The required numbers and locations of axial foci can be designed by generalized Fibonacci photon sieves (GFiPS). Furthermore, the three-dimensional array foci can be controllable and adjustable by the optical path difference scaling factor (OPDSF) when the amplitude modulation is replaced with the phase modulation. Multi-focal technologies can be applied to nano-imaging, THZ, laser communications, direct laser writing, optical tweezers or atom trapping, etc.

  20. Human intestinal circadian clock: expression of clock genes in colonocytes lining the crypt.

    Science.gov (United States)

    Pardini, L; Kaeffer, B; Trubuil, A; Bourreille, A; Galmiche, J-P

    2005-01-01

    Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.

  1. Exploration of chromatic aberration for multiplanar imaging: proof of concept with implications for fast, efficient autofocus.

    Science.gov (United States)

    Weinigel, Martin; Kellner, Albert L; Price, Jeffrey H

    2009-12-01

    Image-based autofocus determines focus directly from the specimen (as opposed to reflective surface positioning with an offset), but sequential acquisition of a stack of images to measure resolution/sharpness and find best focus is slower than reflective positioning. Simultaneous imaging of multiple focal planes, which is also useful for 3D imaging of live cells, is faster but requires complicated optics. With color CCD cameras and white light sources commonly available, we asked if axial chromatic aberration can be utilized to acquire multiple focal planes simultaneously, and if it can be controlled through a range sufficient for practical use. For proof of concept, we theoretically and experimentally explored the focal differences between three narrow wavelength bands on a 3-chip color CCD camera with and without glass inserts of various thicknesses and dispersions. Ray tracing yielded changes in foci of 0.65-0.9 microm upon insertion of 12.5-mm thick glass samples for green (G, 522 nm) vs. blue (B, 462 nm) and green vs. red (G-R, 604 nm). On a microscope: (1) With no glass inserts, the differences in foci were 2.15 microm (G-B) and 0.43 microm (G-R); (2) With glass inserts, the maximum change in foci for G vs. B was 0.44 microm and for G vs. R was 0.26 microm; and (3) An 11.3 mm thick N-BK7 glass insert shifted the foci 0.9 microm (R), 0.6 microm (G), and 0.35 microm (B), such that the B and R foci were farther apart (2.1 microm vs. 1.7 microm) and the R and G foci were closer together (0.25 microm vs. 0.45 microm). The slopes of the differences in foci were dependent on thickness, index of refraction, and dispersion. The measured differences in foci are comparable to the axial steps of 0.1-0.24 microm commonly used for autofocus, and focal plane separation can be altered by inserting optical elements of various dispersions and thicknesses. By enabling acquisition of multiple, axially offset images simultaneously, chromatic aberration, normally an imaging pariah

  2. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Science.gov (United States)

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine.

  3. Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases.

    Science.gov (United States)

    Reid, Michelle D; Basturk, Olca; Shaib, Walid L; Xue, Yue; Balci, Serdar; Choi, Hye-Jeong; Akkas, Gizem; Memis, Bahar; Robinson, Brian S; El-Rayes, Bassel F; Staley, Charles A; Staley, Christopher A; Winer, Joshua H; Russell, Maria C; Knight, Jessica H; Goodman, Michael; Krasinskas, Alyssa M; Adsay, Volkan

    2016-10-01

    High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy

  4. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    Science.gov (United States)

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  5. Instabilities of monolayered epithelia: shape and structure of villi and crypts

    CERN Document Server

    Hannezo, Edouard; Joanny, Jean-Francois; 10.1103/PhysRevLett.107.078104

    2012-01-01

    We study theoretically the shapes of a dividing epithelial monolayer of cells lying on top of an elastic stroma. The negative tension created by cell division provokes a buckling instability at a finite wave vector leading to the formation of periodic arrays of villi and crypts. The instability is similar to the buckling of a metallic plate under compression. We use the results to rationalize the various structures of the intestinal lining observed \\emph{in vivo}. Taking into account the coupling between cell division and local curvature, we obtain different patterns of villi and crypts, which could explain the different morphologies of the small intestine and the colon.

  6. Instabilities of Monolayered Epithelia: Shape and Structure of Villi and Crypts

    Science.gov (United States)

    Hannezo, E.; Prost, J.; Joanny, J.-F.

    2011-08-01

    We study theoretically the shapes of a dividing epithelial monolayer of cells lying on top of an elastic stroma. The negative tension created by cell division provokes a buckling instability at a finite wave vector leading to the formation of periodic arrays of villi and crypts. The instability is similar to the buckling of a metallic plate under compression. We use the results to rationalize the various structures of the intestinal lining observed in vivo. Taking into account the coupling between cell division and local curvature, we obtain different patterns of villi and crypts, which could explain the different morphologies of the small intestine and the colon.

  7. Aberration Correction in Electron Microscopy

    CERN Document Server

    Rose, Harald H

    2005-01-01

    The resolution of conventional electron microscopes is limited by spherical and chromatic aberrations. Both defects are unavoidable in the case of static rotationally symmetric electromagnetic fields (Scherzer theorem). Multipole correctors and electron mirrros have been designed and built, which compensate for these aberrations. The principles of correction will be demonstrated for the tetrode mirror, the quadrupole-octopole corrector and the hexapole corrector. Electron mirrors require a magnetic beam separator free of second-order aberrations. The multipole correctors are highly symmetric telescopic systems compensating for the defects of the objective lens. The hexapole corrector has the most simple structure yet eliminates only the spherical aberration, whereas the mirror and the quadrupole-octopole corrector are able to correct for both aberrations. Chromatic correction is achieved in the latter corrector by cossed electric and magnetic quadrupoles acting as first-order Wien filters. Micrographs obtaine...

  8. Camera processing with chromatic aberration.

    Science.gov (United States)

    Korneliussen, Jan Tore; Hirakawa, Keigo

    2014-10-01

    Since the refractive index of materials commonly used for lens depends on the wavelengths of light, practical camera optics fail to converge light to a single point on an image plane. Known as chromatic aberration, this phenomenon distorts image details by introducing magnification error, defocus blur, and color fringes. Though achromatic and apochromatic lens designs reduce chromatic aberration to a degree, they are complex and expensive and they do not offer a perfect correction. In this paper, we propose a new postcapture processing scheme designed to overcome these problems computationally. Specifically, the proposed solution is comprised of chromatic aberration-tolerant demosaicking algorithm and post-demosaicking chromatic aberration correction. Experiments with simulated and real sensor data verify that the chromatic aberration is effectively corrected.

  9. 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

  10. 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.

  11. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging

    Science.gov (United States)

    Ritsma, Laila; Ellenbroek, Saskia I. J.; Zomer, Anoek; Snippert, Hugo J.; de Sauvage, Frederic J.; Simons, Benjamin D.; Clevers, Hans; van Rheenen, Jacco

    2014-03-01

    The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5+ cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5-Confetti mice. We find that Lgr5+ cells in the upper part of the niche (termed `border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed `central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5+ cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.

  12. 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 t

  13. 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.

  14. Features of direct implantation in chronic foci of odontogenic infection

    Directory of Open Access Journals (Sweden)

    Gudaryan А.А.

    2016-12-01

    Full Text Available The article presents the results of the developed therapeutic and prophylactic complex and efficacy of immediate implantation in 66 patients with chronic foci of odontogenic infection in the periapical region. Objective: to increase preventive measures of inflammatory and infectious complications and optimization of osteo-integrative processes in immediate implantation after tooth extraction, with periapical foci of chronic infection. It was found that the use of the developed medical complex of following up direct implantation includes the use of local photodynamic therapy, platelet, rich in fibrin as a injection and membranes; this allowed to create a favorable background for the prevention of inflammatory and infectious complications in the peri-implant area and created a favorable background for the osseo-integration of implants in 97.1% of the investigated.

  15. [The implantation of bipolar coagulation to remove endometriosis foci].

    Science.gov (United States)

    Sobkiewicz, S; Palatyński, A; Salata, I

    2001-05-01

    The paper compares the results of bipolar coagulation bey means of ERBE ICC 300 diatermy coagulator and WISAP endocoagulator. The results of both types of coagulation were assessed with reference to the changes occurring on peritoneum ligamenti sacro-uterini, Douglas pouch and ovary. The best results of endometriosis foci coagulation were obtained with bipolar ball at 20-30 W; no side effects or feelings of malaise were observed in patients just after the operation or over a longer period of convalescence.

  16. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

    Directory of Open Access Journals (Sweden)

    Sripathi M Sureban

    Full Text Available Gastrointestinal (GI mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC marker, 24h after high dose total-body gamma-IR (TBI can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR-induced intestinal stem cell (ISC deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death. Animals were exposed to TBI (14 Gy and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d, and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

  17. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

    Science.gov (United States)

    Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

    2015-01-01

    Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

  18. Acanthomatous ameloblastoma with atypical foci in five dogs.

    Science.gov (United States)

    Malmberg, Jennifer L; Howerth, Elizabeth W; Powers, Barb E; Schaffer, Paula A

    2017-03-01

    Acanthomatous ameloblastoma is a common, locally invasive, nonmetastasizing tumor of the canine oral cavity. The long-term prognosis for canine acanthomatous ameloblastoma is good if complete excision can be achieved, usually by maxillectomy or mandibulectomy. A variant of acanthomatous ameloblastoma with atypical foci was noted in 5 dogs. There was no age, breed, or sex predisposition. Atypical cells were pleomorphic with a high mitotic rate. They were immunohistochemically negative for cytokeratin, vimentin, melan A, PNL2, CD3, Pax5, CD18, chromogranin A, and synaptophysin. Ultrastructurally, the atypical cells had modest amounts of electron-lucent cytoplasm, abundant rough endoplasmic reticulum, zonula adherens junctions, cleaved or irregular nuclei, and occasional cytoplasmic structures consistent with secretory granules or lysosomes. Complete excision was achieved by maxillectomy or mandibulectomy in 3 dogs; the lesion was incompletely excised in 2 dogs. No ancillary therapy was elected in any patient. No local recurrence or distant metastasis was reported in any case. One patient died of heart failure 20 mo following complete excision; all other patients were alive at last follow-up (average follow-up: 18.8 mo, range: 6-30 mo). The histogenesis of the atypical foci is unclear, but atypical foci within acanthomatous ameloblastoma do not appear to be associated with metastasis or with a poor prognosis relative to acanthomatous ameloblastoma with typical histologic morphology.

  19. 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.

  20. 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

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......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...

  1. Phase aberration effects in elastography.

    Science.gov (United States)

    Varghese, T; Bilgen, M; Ophir, J

    2001-06-01

    In sonography, phase aberration plays a role in the corruption of sonograms. Phase aberration does not have a significant impact on elastography, if statistically similar phase errors are present in both the pre- and postcompression signals. However, if the phase errors are present in only one of the pre- or postcompression signal pairs, the precision of the strain estimation process will be reduced. In some cases, increased phase errors may occur only in the postcompression signal due to changes in the tissue structure with the applied compression. Phase-aberration effects increase with applied strain and may be viewed as an image quality derating factor, much like frequency-dependent attenuation or undesired lateral tissue motion. In this paper, we present a theoretical and simulation study of the effects of phase aberration on the elastographic strain-estimation process, using the strain filter approach.

  2. Historical aspects of aberration correction.

    Science.gov (United States)

    Rose, Harald H

    2009-06-01

    A brief history of the development of direct aberration correction in electron microscopy is outlined starting from the famous Scherzer theorem established in 1936. Aberration correction is the long story of many seemingly fruitless efforts to improve the resolution of electron microscopes by compensating for the unavoidable resolution-limiting aberrations of round electron lenses over a period of 50 years. The successful breakthrough, in 1997, can be considered as a quantum step in electron microscopy because it provides genuine atomic resolution approaching the size of the radius of the hydrogen atom. The additional realization of monochromators, aberration-free imaging energy filters and spectrometers has been leading to a new generation of analytical electron microscopes providing elemental and electronic information about the object on an atomic scale.

  3. [Possibilities of ultrasonic investigations in differentiation of a small-foci impairment of thyroid gland].

    Science.gov (United States)

    Reyti, A O; Vityuk, N V; Medvedev, V E; Starushok, I O

    2015-03-01

    The results of ultrasound investigation of microcarcinomas and nontumoral foci of thyroid gland up to 10 mm in diameter and malignant foci over 10 mm are presented. Ultrasound signs are depicted, in accordance to which a potentially malignant thyroid gland foci are delineated, what demands a morphological (cytological) verification conduction.

  4. 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.

  5. Three dimensional analysis of chromatic aberration in diffractive elements with extended depth of focus.

    Science.gov (United States)

    Mas, D; Espinosa, J; Perez, J; Illueca, C

    2007-12-24

    The paper presents the polychromatic analysis of two diffractive optical elements with extended depth of focus: the linear axicon and the light sword optical element. Chromatic aberration produces axial displacement of the focal segment line. Thus, we explore the possibility of extending the focal depth of these elements to permit superposition of the chromatic foci. In the case of an axicon, we achieve an achromatic zone where focusing is produced. In the case of the light sword element, we show that the focusing segment is out of axis. Therefore a superposition of colors is produced, but not on axis overlapping. Instead, three colored and separated foci are simultaneously obtained in a single plane. Three dimensional structures of the propagated beams are analyzed in order to provide better understanding of the properties and applications of such elements.

  6. Detecting and localizing the foci in human epileptic seizures

    CERN Document Server

    Ben-Jacob, E; Pomyalov, A; Procaccia, I; Towle, V L; Ben-Jacob, Eshel; Boccaletti, Stefano; Pomyalov, Anna; Procaccia, Itamar; Towle, Vernon L.

    2007-01-01

    We consider the electrical signals recorded from a subdural ECoG grid of electrodes placed on the pial surface of the brain for chronic evaluation of epileptic patients before surgical resection. A simple and computationally fast method to analyze the inter-ictal phase synchrony between such electrodes is introduced and developed with the aim of detecting and localizing the foci of the epileptic events. We evaluate the method by comparing the results of surgery to the localization predicted here. We find an indication of good correspondence between the success or failure in the surgery and the agreement between our identification and the regions actually operated on.

  7. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    Science.gov (United States)

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  8. Auxerre, la crypte de la cathédrale Saint-Étienne

    Directory of Open Access Journals (Sweden)

    Christian Sapin

    2004-12-01

    Full Text Available Les investigations sur les élévations intérieures de la crypte romane, construite dans le second quart du XIe siècle par l’évêque Hugues de Chalon, ont repris au cours d’une campagne en juin 2003. Celle-ci a également entamé une reconnaissance des sols à l’extérieur de l’accès sud de la crypte. En effet, en 2002, nous avions montré que la salle centrale n’était pas accessible à l’origine par les escaliers construits à l’ouest, beaucoup plus tard à la fin du XIe siècle, et que les accès se fai...

  9. 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.

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

    Science.gov (United States)

    Amo-Takyi, B K; Mittermayer, C; Günther, 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 α-satellite probes for chromosomes 3, 7 or 17. Particular preference was given to cases which had separate foci with different cytomorphologies. Furthermore, we compared aberrations in relation to tumour size, stage, grade and between different foci in a specimen. Thirty-four cases had multiple tumours. Forty-seven per cent of the multicentric tumours were conventional RCCs and 53% papillary RCTs (against 83% solitary conventional RCCs and 5% solitary papillary RCTs). Three conventional RCCs sized 8 mm (G3), 13 cm (pT2, G2) and 15 cm (pT3b, G3), respectively, revealed monosomy 3, and 13 were disomic. Seventeen papillary RCTs (11 carcinomas and six adenomas) displayed trisomy 17, irrespective of size or grade. Four papillary carcinomas and six papillary adenomas had trisomy 7, and the rest (seven papillary carcinomas and one papillary adenoma) revealed disomy 7. In conclusion, papillary RCTs were tendentially multicentric. Although specific for conventional RCCs heedless of size, monosomy 3 was only observed in high-grade and/or advanced tumours. Trisomy 17 was only detectable in papillary RCTs irrespective of tumour state, showing increased copies with tumour growth. Papillary RCTs also appeared to lose some copies of chromosome 7 with tumour progress, possibly reflecting malignancy. © 2000 Cancer Research Campaign PMID:10780519

  11. Fibroblast growth factor receptor-3 is expressed in undifferentiated intestinal epithelial cells during murine crypt morphogenesis.

    Science.gov (United States)

    Vidrich, Alda; Buzan, Jenny M; Ilo, Chibuzo; Bradley, Leigh; Skaar, Kirstin; Cohn, Steven M

    2004-05-01

    Prior studies have demonstrated that fibroblast growth factor receptor-3 (FGFR-3) regulates proliferation of undifferentiated intestinal epithelial cells in vitro. However, the function(s) of FGFR-3-mediated signaling during intestinal development and epithelial differentiation in vivo remain unknown. The goal of this study was to define the temporal, regional, and cell-specific patterns of FGFR-3 expression and its ligands during normal intestinal ontogeny and epithelial regeneration. Both the IIIb and IIIc isoforms of FGFR-3 mRNA, which result from differential splicing of the FGFR-3 primary transcript, were detected in mouse small intestine as early as embryonic day 16. FGFR-3 levels peaked in the small intestine from 7 to 21 days after birth and decreased thereafter to reach the low levels observed in adult mice. FGFR-3 IIIb and IIIc mRNA levels were highest in the duodenum and proximal jejunum with lower levels of both seen in the distal jejunum, ileum, and colon. FGFR-3 was expressed in a subset of proliferating undifferentiated crypt epithelial cells located in the intervillous epithelium and in the lower half of nascently forming crypts but not in differentiated epithelial cell types. FGFR-3 IIIb was the dominant isoform expressed in both small intestinal and colonic crypts. Expression of FGF1, FGF2, and FGF9, known ligands of FGFR-3, paralleled patterns of FGFR-3 expression during gut development. These data suggest that signaling through FGFR-3 plays a role in regulating morphogenic events involved in formation of intestinal crypts and/or the fate of epithelial stem cells.

  12. 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.

  13. 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

  14. Analysis of the spatial and dynamical properties of a multiscale model of intestinal crypts

    Directory of Open Access Journals (Sweden)

    Marco Antoniotti

    2013-09-01

    Full Text Available The preliminary analyses on a multiscale model of intestinal crypt dynamics are here presented. The model combines a morphological model, based on the Cellular Potts Model (CPM, and a gene regulatory network model, based on Noisy Random Boolean Networks (NRBNs. Simulations suggest that the stochastic differentiation process is itself sufficient to ensure the general homeostasis in the asymptotic states, as proven by several measures.

  15. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence.

    Science.gov (United States)

    Sørensen, Mads V; Strandsby, Anne B; Larsen, Casper K; Praetorius, Helle A; Leipziger, Jens

    2011-11-01

    The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na(+) absorption and K(+) secretion. The electrogenic Na(+) absorption is mediated by epithelial Na(+) channel (ENaC) in surface cells. Previously, we identified the large conductance Ca(2+)-activated K(+) channel, K(Ca)1.1 or big potassium (BK) channel, as the only relevant K(+) secretory pathway in mouse distal colon. The exact localisation of K(Ca)1.1 channels along the crypt axis is, however, still controversial. The aim of this project was to further define the localisation of the K(Ca)1.1 channel in mouse distal colonic epithelium. Through quantification of mRNA extracted from micro-dissected surface and crypt cells, we confirmed that Na(+)/K(+)/2Cl(-) (NKCC1) is expressed primarily in the crypts and γ-ENaC primarily in the surface cells. The K(Ca)1.1 α-subunit mRNA was like NKCC1, mainly expressed in the crypts. The crypt to surface expression pattern of the channels and transporters was not altered when plasma aldosterone was elevated. The mRNA levels for NKCC1, γ-ENaC and K(Ca)1.1 α-subunit were, however, under these circumstances substantially augmented (K(Ca)1.1 α-subunit, twofold; NKCC1, twofold and ENaC, tenfold). Functionally, we show that ENaC-mediated Na(+) absorption and BK channel-mediated K(+) secretion are two independent processes. These findings show that K(Ca)1.1-mediated K(+) secretion mainly occurs in the crypts of the murine distal colon. This is in agreement with the general model of ion secretion being preferentially located to the crypt and not surface enterocytes.

  16. Application of Three-Dimensional Imaging to the Intestinal Crypt Organoids and Biopsied Intestinal Tissues

    Directory of Open Access Journals (Sweden)

    Yun Chen

    2013-01-01

    Full Text Available Two-dimensional (2D histopathology is the standard analytical method for intestinal biopsied tissues; however, the role of 3-dimensional (3D imaging system in the analysis of the intestinal tissues is unclear. The 3D structure of the crypt organoids from the intestinal stem cell culture and intestinal tissues from the donors and recipients after intestinal transplantation was observed using a 3D imaging system and compared with 2D histopathology and immunohistochemistry. The crypt organoids and intestinal tissues showed well-defined 3D structures. The 3D images of the intestinal tissues with acute rejection revealed absence of villi and few crypts, which were consistent with the histopathological features. In the intestinal transplant for megacystis microcolon intestinal hypoperistalsis syndrome, the donor’s intestinal tissues had well-developed nerve networks and interstitial cells of Cajal (ICCs in the muscle layer, while the recipient’s intestinal tissues had distorted nerve network and the ICCs were few and sparsely distributed, relative to those of the donor. The 3D images showed a clear spatial relationship between the microstructures of the small bowel and the features of graft rejection. In conclusion, integration of the 3D imaging and 2D histopathology provided a global view of the intestinal tissues from the transplant patients.

  17. Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis

    Science.gov (United States)

    Yang, Huansheng; Wang, Xiaocheng; Xiong, Xia; Yin, Yulong

    2016-01-01

    Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets. PMID:27558220

  18. Inhibition of Notch signaling reduces the number of surviving Dclk1+ reserve crypt epithelial stem cells following radiation injury.

    Science.gov (United States)

    Qu, Dongfeng; May, Randal; Sureban, Sripathi M; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ali, Naushad; Li, Linheng; Barrett, Terrence; Houchen, Courtney W

    2014-03-01

    We have previously reported that doublecortin-like kinase 1 (Dclk1) is a putative intestinal stem cell (ISC) marker. In this report, we evaluated the use of Dclk1 as a marker of surviving ISCs in response to treatment with high-dose total body irradiation (TBI). Both apoptotic and mitotic Dclk1(+) cells were observed 24 h post-TBI associated with a corresponding loss of intestinal crypts observed at 84 h post-TBI. Although the Notch signaling pathway plays an important role in regulating proliferation and lineage commitment within the intestine, its role in ISC function in response to severe genotoxic injury is not yet fully understood. We employed the microcolony assay to functionally assess the effects of Notch inhibition with difluorophenacetyl-l-alanyl-S-phenylglycine t-butyl ester (DAPT) on intestinal crypt stem cell survival following severe (>8 Gy) radiation injury. Following treatment with DAPT, we observed a nearly 50% reduction in the number of surviving Dclk1(+) crypt epithelial cells at 24 h after TBI and similar reduction in the number of surviving small intestinal crypts at 84 h. These data indicate that inhibition of Notch signaling decreases ISC survival following radiation injury, suggesting that the Notch signaling pathway plays an important role in ISC-mediated crypt regeneration. These results also suggest that crypt epithelial cell Dclk1 expression can be used as one potential marker to evaluate the early survival of ISCs following severe radiation injury.

  19. Experimentally observe the effect of spherical aberration on diffractive intraocular lens using adaptive optics

    Science.gov (United States)

    Guo, Huanqing; DeLestrange, Elie

    2015-03-01

    We first investigated the similarity in optical quality of a batch of diffractive intraocular lenses (DIOLs), providing experimental evidence for one DIOL as representative of a batch. Using adaptive optics, we then evaluated one DIOL under different levels of Zernike spherical aberration (SA) by applying both a point spread function test and a psychophysical visual acuity test. We found that for small aperture size SA has the effect of shifting the through-focus curve of DIOL. Also, for a relatively large aperture size, it has different effects on the distant and near foci.

  20. [Monitoring the natural foci of tularemia on Wrangel Island].

    Science.gov (United States)

    Podobedova, Ia S; Meshcheriakova, I S; Demidova, T N; Kormilitsyna, M I; Mikhaĭlova, T V; Baraniuk, V V

    2013-01-01

    Long-term annual monitoring of the natural foci of tularemia was first made on Wrangel Island. The objects of the investigation were pellets of birds-myophages, blood samples from rodents, and excrements from carnivorous mammals. A total of 2626 biological samples were examined in the period 2002 to 2011. A serological test was ascertained to be the most effective method for the detection of tularemia epizooties; polymerase chain reaction should be used as an additional technique to examine blood samples, as well as rodent tubular bone debris taken from the pellets. Tularemia epizooties were registered in the populations of two species of lemmings every year, except in 2003. An intensive diffuse tularemia epizooty was first detected in this area, which emerged in 2019, peaked by spring 2011, and covered most of the island. The antigen of tularemia pathogen was identified in 43.46% of the samples under examination,which is a high quantitative indicator of the intensity of an epizootic process. The fact that positive samples are annually found in the same areas of the island suggests that the causative agent is steadily and long preserved in the parasitic system. The availability of stable and active natural tularemia foci on Wrangel Island calls for preventive measures, particularly vaccination of risk groups coming to the island to conduct researches.

  1. Quantitative analysis of crypt cell population during postnatal development of the olfactory organ of the guppy, Poecilia reticulata (Teleostei, Poecilidae), from birth to sexual maturity.

    Science.gov (United States)

    Bettini, Simone; Lazzari, Maurizio; Franceschini, Valeria

    2012-08-01

    Crypt cells are one of three types of olfactory sensory neuron, differing from ciliated and microvillar cells in shape, localization and number, and found only in fish. Although crypt cells are morphologically well characterized, their function remains unclear. They were hypothesized to be involved in reproductive behaviours by detecting sex pheromones, but electrophysiological investigations revealed sensitivity to only amino acids. However, the number of crypt cells in adult guppies is not the same in the two sexes. In this study, we compared the size of the crypt cell population in juvenile guppies during the first 90 days after birth. The purpose of our study was to clarify whether a correlation exists between sex and the number of these olfactory neurons. The data show that guppies reach adult crypt cell density when they become sexually mature. Despite a constant increment in volume during development of the olfactory organ, the minimum density of crypt neurons occurs at ~45 days. Moreover, in the early weeks, the density of crypt neurons is greater in males than in females because in females the total number of cells decreases significantly after just 7 days. In adults, however, crypt neurons are found in higher density in females than in males. These findings suggest that the number of crypt cells is sex specific, with independent developmental dynamics between males and females. A role in pheromone detection could explain such a difference, but the early appearance of crypt cells in the first days of life is suggestive of other, not sexually related, functions.

  2. Surveillance of endemic foci of tick-borne encephalitis in Finland 1995-2013: evidence of emergence of new foci.

    Science.gov (United States)

    Tonteri, Elina; Kurkela, Satu; Timonen, Suvi; Manni, Tytti; Vuorinen, Tytti; Kuusi, Markku; Vapalahti, Olli

    2015-01-01

    The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.

  3. Smad3 contributes to positioning of proliferating cells in colonic crypts by inducing EphB receptor protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa, Kiyoshi [Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Sato, Toru [Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Katsuno, Tatsuro, E-mail: katsuno@faculty.chiba-u.jp [Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Nakagawa, Tomoo; Noguchi, Yoshiko [Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Tokumasa, Atsuko; Yokote, Kotaro [Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan); Saito, Yasushi [Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670 (Japan)

    2011-02-25

    Research highlights: {yields} Smad3{sup -/-} mice showed an increased number of proliferating epithelial cells in colonic crypts. {yields} Proliferating epithelial cells showed activated Wnt/{beta}-catenin pathway. {yields} Smad3{sup -/-} mice also showed intermingling of proliferating cells with differentiated cells. {yields} Loss of EphB receptor expression was observed in the colonic crypts of Smad3{sup -/-} mice. {yields} Loss of EphB receptor expression is likely responsible for cell intermingling. -- Abstract: Deficiency of Smad3, an intracellular mediator of TGF-{beta}, was shown to significantly accelerate re-epithelialization of the colonic mucosa. This study was performed to investigate the molecular mechanisms by which Smad3 controls colonic epithelial cell proliferation and crypt formation. Smad3{sup ex8/ex8} C57BL/6 mice were used in this study and wild-type littermates served as controls. The number of proliferating cells in the isolated colonic epithelium of Smad3{sup -/-} mice was significantly increased compared to that in wild-type littermates. Protein levels of the cell cycle inhibitors p21 and p27 were significantly decreased, while that of c-Myc was increased in the isolated colonic epithelium from Smad3{sup -/-} mice. In the colonic tissue of wild-type mice, cell proliferation was restricted to the bottom of the crypts in accordance with nuclear {beta}-catenin staining, whereas proliferating cells were located throughout the crypts in Smad3{sup -/-} mice in accordance with nuclear {beta}-catenin staining, suggesting that Smad3 is essential for locating proliferating cells at the bottom of the colonic crypts. Notably, in Smad3{sup -/-} mice, there was loss of EphB2 and EphB3 receptor protein expression, critical regulators of proliferating cell positioning, while EphB receptor protein expression was confirmed at the bottom of the colonic crypts in wild-type mice. These observations indicated that disturbance of the EphB/ephrin B system brings

  4. Ultramicrostructure and clinical implications of satellite foci in front of the head of pterygium

    Institute of Scientific and Technical Information of China (English)

    LIU Haixia; XIANG Nan; ZHOU Xiongwu; HU Weikun; LI Guigang; ZHANG Hong

    2007-01-01

    In our previous studies,grey satellite foci were found in the front of heads of pterygia.This research was designed to investigate the ultramicrostructure and clinical implications of these satellite foci.The satellite foci were observed and counted under slit lamp biomicroscope.The patients with eye pterygia were divided into groups in terms of occupation,sex,age,length of history,grade of congestion,and size of the heads.The SPSS 13.0 software was used for statistical analysis.The cap areas and satellite foci were ultramicrostructurally examined.Among the total 62 eyes with pterygium,satellite foci were found in 34.The overall incidence of satellite foci was 54.8%.There were no significant differences in incidence among the subjects of different sex,age,and length of history.There were significant differences in incidence among the patients of different occupation,grades of congestion,and size of heads.Higher grades of congestion,outdoor occupations and larger pterygium heads were associated with higher incidence of satellite foci.High grades of congestion and bigger heads were also correlated with the number of satellite foci.Length of history bore no correlation with number of satellite foci.Histologically,the components of the cap areas and the foci were identical,with both consisting of mass of active fibroblasts.The activated fibroblasts existed in the natural tissue planes between Bowman's layer and basal cell layer.The fibroblasts in the satellite foci and the cap areas of a pterygium show some features of tumor cells and may play a vital role in the development and progression of a pterygium.The presence and amount of satellite foci around a pterygium can be used as an indicator for the speed of its growth.

  5. The mathematics of mosaic analysis. II. Formulae for interacting foci.

    Science.gov (United States)

    Wyman, R J; Salkoff, L

    1982-04-01

    Mosaic fate mapping requires first a measurement of the frequency of separation (by genotype) of two structures and then a conversion of this frequency of separation to distance (WYMAN and THOMAS 1982). If the genotype of two structures is visible, the frequency of separation (sturt distance) may be directly obtained. If the genotype is not visible (e.g., for behavioral foci) then the frequency of separation (sturt distance) itself must be calculated. The formulae introduced by HOTTA and BENZER (1972) for calculating frequency of separation are appropriate only for a set of mosaics in which each fly has half normal and half mutant tissue. Using these formulae for a set of mosaics with a different fraction of mutant tissue can give enormously incorrect results.--In this paper we use intuitive lines of reasoning to obtain simple formulae for frequencies of separation that are algebraically equal to the more elaborate HOTTA and BENZER (1972) formulae.--We show that when calculating sturt distances, data from a collection of mosaics with a range of malenesses, even if the average maleness is 1/2, cannot be lumped together. We prove that applying any formula appropriate for m = 1/2 to a set of mosaics all of maleness m, and then to a set of maleness 1-m, and then averaging the two results, does give the correct value for sturt distances. In this way all the mapping distances may be obtained.--Another method for locating foci is called "contour mapping". We show that the currently available contour formulae are inaccurate. We suggest that contour maps be drawn using the accurate sturt distances.

  6. Using geometric algebra to study optical aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, J.; Ziock, H.

    1997-05-01

    This paper uses Geometric Algebra (GA) to study vector aberrations in optical systems with square and round pupils. GA is a new way to produce the classical optical aberration spot diagrams on the Gaussian image plane and surfaces near the Gaussian image plane. Spot diagrams of the third, fifth and seventh order aberrations for square and round pupils are developed to illustrate the theory.

  7. 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.

  8. 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

    2015-07-01

    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-EGFP(Low)) and reserve/facultative ISCs (Sox9-EGFP(High)) 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-EGFP(Low) ISCs and percentage of these cells in M-phase. IGF1 increased percentages of Sox9-EGFP(High) 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-EGFP(High) facultative ISCs but not Sox9-EGFP(Low) 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.

  9. Hierarchy and plasticity in the crypt: back to the drawing board

    Institute of Scientific and Technical Information of China (English)

    Catherine Legraverend; Philippe Jay

    2011-01-01

    The prevailing concept in the field of stem cell research is that of a multipotent self-renewing cell,positioned at the origin of a hierarchical tree of branching specificities,increasing maturity and decreasing self-renewal ability.In the epithelium of the small intestine,until very recently,the supra-Paneth crypt base columnar (CBC) cell position +4(cp4) (counting from the bottom of the crypt) was widely assumed to be the preferred position of multipotent stem cells [1,2].Yet electron microscopy,as well as autoradiography and lineage tracing studies,supported the presence of undifferentiated [3],actively cycling [4],multipotent CBC stem cells located between Paneth cells in the crypt [5-7].Based on the results of expression and lineage studies with Lgr5-EGFP-IRES-CreERT2 knock-in mice and Rosa26-LacZ reporter mice,it was possible to show that multipotent CBC cells expressing the Lgr5 orphan receptor are present throughout the gastro-intestinal tract [7].But they are not alone.Another recent lineage study revealed the existence of multipotent,self-renewing Lgr5- CBC cells expressing the Bmi1 proto-oncogene and preferentially located above the highest Paneth cell [8].This discovery brought the cp4 model back under the spotlight,and subsequent expression studies revealed a partial overlap between the Lgr5+ and Bmi1+ CBC cell populations [9].In a recent issue of Nature,Huan Tian and colleagues now tackle the issue of their contribution to the turnover of the intestinal epithelium [10].

  10. Regulation of Ceramide Synthase-Mediated Crypt Epithelium Apoptosis by DNA Damage Repair Enzymes

    Science.gov (United States)

    Rotolo, Jimmy A.; Mesicek, Judith; Maj, Jerzy; Truman, Jean-Philip; Haimovitz-Friedman, Adriana; Kolesnick, Richard; Fuks, Zvi

    2015-01-01

    Acute endothelial cell apoptosis and microvascular compromise couple GI tract irradiation to reproductive death of intestinal crypt stem cell clonogens (SCCs) following high-dose radiation. Genetic or pharmacologic inhibition of endothelial apoptosis prevents intestinal damage, but as the radiation dose is escalated, SCCs become directly susceptible to an alternate cell death mechanism, mediated via ceramide synthase (CS)-stimulated de novo synthesis of the pro-apoptotic sphingolipid ceramide, and p53-independent apoptosis of crypt SCCs. We previously reported that ATM deficiency resets the primary radiation lethal pathway, allowing CS-mediated apoptosis at the low-dose range of radiation. The mechanism for this event, termed target reordering, remains unknown. Here we show that inactivation of DNA damage repair pathways signal CS-mediated apoptosis in crypt SCCs, presumably via persistent unrepaired DNA double strand breaks (DSBs). Genetic loss-of-function of sensors and transducers of DNA DSB repair confers the CS-mediated lethal pathway in intestines of sv129/B6Mre11ATLD1/ATLD1 and C57BL/6Prkdc/SCID (SCID) mice exposed to low-dose radiation. In contrast, CS-mediated SCC lethality was mitigated in irradiated gain-of-function Rad50S/S mice, and epistasis studies order Rad50 upstream of Mre11. These studies suggest unrepaired DNA DSBs as causative in target re-ordering in intestinal SCCs. As such, we provide an in vivo model of DNA damage repair that is standardized, can be exploited to understand allele-specific regulation in intact tissue, and is pharmacologically tractable. PMID:20086180

  11. 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.

  12. Correlations between corneal and total wavefront aberrations

    Science.gov (United States)

    Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

    2002-06-01

    Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

  13. [Evolution of hyperplastic foci in the rat liver induced by diethylnitrosamine].

    Science.gov (United States)

    Gel'shteĭn, V I; Chipysheva, T A; Bannikov, G A

    1984-01-01

    The immunohistochemical localization of ligandin (L), A-protein (A) and alpha-fetoprotein (AFP) was studied in the liver of rats treated intraperitoneally with diethylnitrosamine (DENA). In early foci of altered cells there was a consecutive change in the content of antigens. The uniform content of L and A in these foci changed for the uniform content of only one marker. Late foci of altered hepatocytes were characterized by a heterogeneous distribution of the markers. 12-14 weeks after the treatment the neoplastic nodules with different antigenic phenotypes dependent on the morphological structure were detected. Cells in neoplastic nodules were uniform as to the marker content. Alpha-fetoprotein was unavailable in foci of altered cells and in neoplastic nodules either. It is concluded that evolution of most of foci follows the way of postnatal maturation similar to that in the normal liver and neoplastic nodules represent a side branch of differentiation blocked at different stages.

  14. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech;

    2011-01-01

    Na+ absorption is mediated by epithelial Na+ channel (ENaC) in surface cells. Previously, we identified the large conductance Ca2+-activated K+ channel, KCa1.1 or big potassium (BK) channel, as the only relevant K+ secretory pathway in mouse distal colon. The exact localisation of K(Ca)1.1 channels...... along the crypt axis is, however, still controversial. The aim of this project was to further define the localisation of the K(Ca)1.1 channel in mouse distal colonic epithelium. Through quantification of mRNA extracted from micro-dissected surface and crypt cells, we confirmed that Na+/K+/2Cl- (NKCC1......The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na+ absorption and K+ secretion. The electrogenic...

  15. Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice

    Science.gov (United States)

    Valverde, M. A.; O'Brien, J. A.; Sepulveda, F. V.; Ratcliff, R. A.; Evans, M. J.; Colledge, W. H.

    1995-09-01

    Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl^- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl^- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl^- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K^+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl^- secretion.

  16. 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.

  17. EP receptor expression in human intestinal epithelium and localization relative to the stem cell zone of the crypts.

    Science.gov (United States)

    Olsen Hult, Lene Th; Kleiveland, Charlotte R; Fosnes, Kjetil; Jacobsen, Morten; Lea, Tor

    2011-01-01

    There is substantial evidence for PGE2 affecting intestinal epithelial proliferation. PGE2 is also reported to be involved in the regulation of growth and differentiation in adult stem cells, both effects mediated by binding to EP-receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX expression in human intestinal epithelial cells with focus on the stem cell area of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies from patients with untreated celiac disease, were investigated by immunohistochemistry and RT-PCR. The combination of fresh flash-frozen tissue and laser microdissection made it possible to isolate RNA from the epithelial cell layer, only. In the small intestine, Lgr5 labels cells are in the +4 position, while in the colon, Lgr5 positive cells are localized to the crypt bottoms. Epithelial crypt cells of normal small intestine expressed neither EP-receptor mRNA nor COX1/2. However, crypt cells in tissue from patients with untreated celiac disease expressed EP2/4 receptor and COX1 mRNA. In the colon, the situation was different. Epithelial crypt cells from normal colon were found to express EP2/4 receptor and COX1/2 transcripts. Thus, there are distinct differences between normal human small intestine and colon with regard to expression of EP2/4 receptors and COX1/2. In normal colon tissue, PGE2-mediated signaling through EP-receptors 2/4 could be involved in regulation of growth and differentiation of the epithelium, while the lack of EP-receptor expression in the small intestinal tissue exclude the possibility of a direct effect of PGE2 on the crypt epithelial cells.

  18. EP receptor expression in human intestinal epithelium and localization relative to the stem cell zone of the crypts.

    Directory of Open Access Journals (Sweden)

    Lene Th Olsen Hult

    Full Text Available There is substantial evidence for PGE2 affecting intestinal epithelial proliferation. PGE2 is also reported to be involved in the regulation of growth and differentiation in adult stem cells, both effects mediated by binding to EP-receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX expression in human intestinal epithelial cells with focus on the stem cell area of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies from patients with untreated celiac disease, were investigated by immunohistochemistry and RT-PCR. The combination of fresh flash-frozen tissue and laser microdissection made it possible to isolate RNA from the epithelial cell layer, only. In the small intestine, Lgr5 labels cells are in the +4 position, while in the colon, Lgr5 positive cells are localized to the crypt bottoms. Epithelial crypt cells of normal small intestine expressed neither EP-receptor mRNA nor COX1/2. However, crypt cells in tissue from patients with untreated celiac disease expressed EP2/4 receptor and COX1 mRNA. In the colon, the situation was different. Epithelial crypt cells from normal colon were found to express EP2/4 receptor and COX1/2 transcripts. Thus, there are distinct differences between normal human small intestine and colon with regard to expression of EP2/4 receptors and COX1/2. In normal colon tissue, PGE2-mediated signaling through EP-receptors 2/4 could be involved in regulation of growth and differentiation of the epithelium, while the lack of EP-receptor expression in the small intestinal tissue exclude the possibility of a direct effect of PGE2 on the crypt epithelial cells.

  19. Plague foci in Viet Nam: zoological and parasitological aspects.

    Science.gov (United States)

    Suntsov, V V; Huong, L T; Suntsova, N I; Gratz, N G

    1997-01-01

    Reported are the results of studies over the period 1989-94 on host-flea complexes in small mammals and their flea ectoparasites in and around a number of human settlements in Viet Nam in which human cases of plague had been found. Collections were also made in savanna and tropical forest areas within a 10-km radius of the settlements. The greatest numbers of small mammals, for the most part Rattus spp., and of the flea ectoparasite Xenopsylla cheopis were found in inhabited areas. X. cheopis was not found on any feral or sylvan mammal further than 0.6 km from settlements. A possible link between wild and commensal mammals may be provided by the flea Lentistivalius klossi, a specific parasite of squirrels and tree-shrews but also found in very small numbers on commensal rats. No zoonotic foci of plague were found in the immediate vicinity of the villages studied and it is most likely that plague persists in a commensal rat-X. cheopis cycle in and around human settlements in Viet Nam.

  20. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  1. Atom lens without chromatic aberrations

    CERN Document Server

    Efremov, Maxim A; Schleich, Wolfgang P

    2012-01-01

    We propose a lens for atoms with reduced chromatic aberrations and calculate its focal length and spot size. In our scheme a two-level atom interacts with a near-resonant standing light wave formed by two running waves of slightly different wave vectors, and a far-detuned running wave propagating perpendicular to the standing wave. We show that within the Raman-Nath approximation and for an adiabatically slow atom-light interaction, the phase acquired by the atom is independent of the incident atomic velocity.

  2. The misalignment induced aberrations of TMA telescopes.

    Science.gov (United States)

    Thompson, Kevin P; Schmid, Tobias; Rolland, Jannick P

    2008-12-08

    The next major space-borne observatory, the James Webb Space Telescope, will be a 6.6M field-biased, obscured, three-mirror anastigmat (TMA). Over the used field of view, the performance of TMA telescopes is dominated by 3(rd) order misalignment aberrations. Here it is shown that two dominant 3(rd) order misalignment aberrations arise for any TMA telescope. One aberration, field constant 3(rd) order coma is a well known misalignment aberration commonly seen in two-mirror Ritchey Chretien telescopes. The second aberration, field-asymmetric, field-linear, 3(rd) order astigmatism is a new and unique image orientation dependence with field derived here for the first time using nodal aberration theory.

  3. Chromatic aberration measurement for transmission interferometric testing.

    Science.gov (United States)

    Seong, Kibyung; Greivenkamp, John E

    2008-12-10

    A method of chromatic aberration measurement is described based on the transmitted wavefront of an optical element obtained from a Mach-Zehnder interferometer. The chromatic aberration is derived from transmitted wavefronts measured at five different wavelengths. Reverse ray tracing is used to remove induced aberrations associated with the interferometer from the measurement. In the interferometer, the wavefront transmitted through the sample is tested against a plano reference, allowing for the absolute determination of the wavefront radius of curvature. The chromatic aberrations of a singlet and a doublet have been measured.

  4. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci.

    Science.gov (United States)

    Dion, Vincent; Kalck, Véronique; Seeber, Andrew; Schleker, Thomas; Gasser, Susan M

    2013-11-01

    The regulation of chromatin mobility in response to DNA damage is important for homologous recombination in yeast. Anchorage reduces rates of recombination, whereas increased chromatin mobility correlates with more efficient homology search. Here we tracked the mobility and localization of spontaneous S-phase lesions bound by Rad52, and find that these foci have reduced movement, unlike enzymatically induced double-strand breaks. Moreover, spontaneous repair foci are positioned in the nuclear core, abutting the nucleolus. We show that cohesin and nucleolar integrity constrain the mobility of these foci, consistent with the notion that spontaneous, S-phase damage is preferentially repaired from the sister chromatid.

  5. 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

    The anatomy of Crenella decussata (Mytiloidea) is described. Individuals of this circumboreal species occupy granular crypts composed of sand grains held in place by mucus. The swollen basal region of the tubule is occupied by an individual, which connects to the sediment surface by two posterior...

  6. Histological and electrophysiological properties of crypt cells from the olfactory epithelium of the marine teleost Trachurus symmetricus.

    Science.gov (United States)

    Schmachtenberg, Oliver

    2006-03-01

    Crypt cells from the olfactory epithelium of the Pacific jack mackerel Trachurus symmetricus were characterized by light and electron microscopy and analyzed in dissociation with the patch-clamp technique in its cell-attached, perforated patch and normal whole-cell mode. Isolated crypt cells remained united with their supporting cells, and both were electrically coupled through gap junctions. Under voltage-clamp, depolarizing voltage steps triggered a transient sodium current, a sustained calcium current, and two types of potassium currents with fast and slow inactivation kinetics. No calcium-dependent potassium current could be observed. The sodium current was blocked by saxitoxin, the calcium current by cobalt and furnidipine, and the potassium currents by tetraethylammonium chloride. In the cell-attached configuration, crypt cells displayed spontaneous spike activity and responded to amino acid solutions with dose-dependent excitation, followed by a period of spike inhibition. These first recordings of individual crypt cells provide the basis for future studies of their odorant specificity, transduction mechanism, and overall function in the fish olfactory epithelium.

  7. 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.

  8. 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...

  9. Three-dimensionally Specific Inhibition of DNA Repair-Related Genes by Activated KRAS in Colon Crypt Model

    Directory of Open Access Journals (Sweden)

    Toshiyuki Tsunoda

    2010-05-01

    Full Text Available Growth and differentiation of colonic epithelium are regulated in the three-dimensional (3D physiological architecture, colonic crypt, and deregulation of 3D interactions is involved in tumorigenesis. Cell-based 3D culture systems provide a suitable approach bridging the gap between two-dimensional (2D culture and animal models. KRAS mutations are found at high frequencies in human colorectal cancer (CRC; however, KRAS-targeted cancer therapy has not been developed. Here, we have established a 3D cell culture model resembling the colonic crypt by use of HKe3 cells, human CRC HCT116 cells disrupted at activated KRAS. In this 3D colonic crypt model, HKe3 cells showed the features of time course-dependent transit-amplifying and terminal-differentiated stages, which are characteristic of normal colonic crypt. On the basis of the features of HCT116 cells, activated KRAS inhibited normal cell polarity and apoptosis in 3D culture. The expression of DNA repair-related tumor suppressor genes including TP53, BRCA1, BRCA2, and EXO-1 was markedly suppressed by activated KRAS in 3D culture but not in 2D culture. These results together suggest that activated KRAS plays critical roles in the accumulation of genetic alterations through inhibition of DNA repair genes and apoptosis and that this 3D culture model will provide a useful tool for investigating the molecular mechanisms of CRC development.

  10. 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.

  11. TrueCrypt加密容器快速检测技术%TrueCrypt Container Fast Detection Technology

    Institute of Scientific and Technical Information of China (English)

    沈长达; 尤俊生; 钱镜洁

    2014-01-01

    TrueCrypt作为目前较为流行的免费开源加密软件之一,在不同平台上得到了广泛的应用。取证过程中经常要对磁盘中的加密文件检测以便进行进一步的解密分析,但由于TrueCrypt加密容器在解密之前不具备任何的签名、结构等特征,因此TrueCrypt加密容器的检测成为了取证过程中的一个难点。目前,还没有精确的TrueCrypt加密容器的检测方法,现有的检测技术主要是通过签名排除结合文件大小信息进行检测。文章在现有检测技术的基础上结合了卡方检验以及信息熵的理论方法,提出了一种TrueCrypt加密容器快速检测技术。该技术不仅能够快速的检测加密容器,而且和现有的检测方法相比检测精确度更高。%TrueCrypt as one of the popular free open source encryption software has been widely applied on different platforms. Forensics process often to detected encrypted ifle for further decrypt and analysis, but TrueCrypt container has no signature and structure, so it is a dififcult to detect TrueCrypt container. In view of the TrueCrypt container ifle, there is no accurate detection method, the available technology is signature rule out combined ifle size limit to detect TrueCrypt container. In this paper, on the basis of the existing detection technology, combined with chi-square test and information entropy theory, we came up with a fast TrueCrypt container detection technology. This method not only can quickly detect TrueCrypt container, but higher precision compared with the existing detection methods.

  12. Polarization Aberrations of Optical Coatings

    Science.gov (United States)

    Jota, Thiago

    This work does not limit itself to its title and touches on a number of related topics beyond it. Starting with the title, Polarization Aberrations of Optical Coatings, the immediate question that comes to mind is: what coatings? All coatings? Not all coatings, but just enough that a third person could take this information and apply it anywhere: to all coatings. The computational work-flow required to break-down the aberrations caused by polarizing events (3D vector forms of reflection and refraction) in dielectric and absorbing materials and for thick and thin films is presented. Therefore, it is completely general and of interest to the wide optics community. The example system is a Ritchey-Chretien telescope. It looks very similar to a Cassegrain, but it is not. It has hyperbolic surfaces, which allows for more optical aberration corrections. A few modern systems that use this configuration are the Hubble Space Telescope and the Keck telescopes. This particular system is a follow-up on this publication, where an example Cassegrain with aluminum coatings is characterized, and I was asked to simply evaluate it at another wavelength. To my surprise, I found a number of issues which lead me to write a completely new, one-of-its-kind 3D polarization ray-tracing code. It can do purely geometrical ray-tracing with add-on the polarization analysis capability, and more importantly: it keeps your data at your fingertips while offering all the outstanding facilities of Mathematica. The ray-tracing code and its extensive library, which can do several advanced computations, is documented in the appendix. The coatings of the Ritchey-Chretien induce a number of aberrations, primarily, but not limited to: tilt, defocus, astigmatism, and coma. I found those forms to exist in both aluminum and with a reflectance-enhancing dielectric quarter-wave multilayer coating over aluminum. The thickness of the film stack varies as function of position to present a quarter-wave of optical

  13. Aberrations of Gradient-Index Lenses.

    Science.gov (United States)

    Matthews, A. L.

    Available from UMI in association with The British Library. In this thesis, the primary aberrations of lenses with a radial focussing gradient-of-index are analysed. Such a lens has a refractive index profile which decreases continuously and radially outward from the optical axis, so that the surfaces of constant refractive index are circular cylinders which are coaxial with the optical axis. Current applications of these lenses include photocopiers, medical endoscopes, telecommunications systems and compact disc systems. Closed formulae for the primary wavefront aberrations for a gradient-index lens with curved or plane entry and exit faces are obtained from the differential equations of such a lens to assess the primary transverse ray aberrations that it introduces. Identical expressions are then obtained by using the difference in optical path length produced between two rays by the lens. This duplication of the derivations of the primary wavefront aberrations acts as a confirmation of the validity of the expressions. One advantage of these equations is that the contributions due to the primary spherical aberration, coma, astigmatism, field curvature and distortion can be assessed individually. A Fortran 77 program has been written to calculate each of these individual contributions, the total primary wavefront aberrations and the primary transverse ray aberrations. Further confirmation of the validity of the expressions is obtained by using this program to show that the coma and distortion were both zero for fully symmetric systems working at unit magnification. The program is then used to assess the primary wavefront aberrations for a gradient-index lens which is currently of interest to the telecommunications industry. These results are compared with values obtained using a finite ray-tracing program for the total wavefront aberrations. This shows that the primary wavefront aberrations are the completely dominant contribution to the total wavefront

  14. Crypts of Hélène Cixous’s Past

    Directory of Open Access Journals (Sweden)

    Nathalie Debrauwere-Miller

    2009-01-01

    Full Text Available Through a reading of Cixous’s Inside (1986, Or: Les lettres de mon père (1997, Reveries of the Wild Woman (2006 and Si Près (2007, this article explores the diverse allegories of “enclosure” in the figure of the crypt containing Cixous’s father. Part of the allegory entails a process of mourning not only for the defunct father but for Algeria as well where he is encrypted. The crypt (father’s cave or tomb as the place and the process of writing imposes the de-cryption of the secret cavities of Cixous’s texts where she is enclosed, inside the father’s cave, in the cavity of his tuberculous lungs, the imagined site from where she writes. The essay focuses on how, with the passage of time, the rapport with the dead father evolves in Cixous’s work and how the figuration of Algeria linked to the disease and death of the father undergoes transformations. The father is described in great detail in Inside and Or, Les lettres de mon père . However in these two early texts, Cixous invents a majestic father incarnating the Law and phallogocentric power as opposed to his condition of a Jew during the Vichy regime, which banned him from practicing his profession and left him powerless. But Cixous never recurs specifically to either identitarian (Jewish or political (Vichy and Algeria values. I assert in this essay that it will not be until her later texts that the father’s tuberculosis becomes a foreshadowing of a Jewish condition in occupied Algeria during the Vichy period.

  15. 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.

  16. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance.

    Science.gov (United States)

    Perry, M E

    1994-08-01

    Material from 25 human palatine tonsils was studied by light microscopy, immunocytochemistry, scanning and transmission electron microscopy. Special attention was focused on the structure of the epithelium lining the tonsillar crypts in the context of its ascribed immunological functions. This epithelium was not uniform and contained patches of stratified squamous nonkeratinising epithelium and patches of reticulated sponge-like epithelium. The degree of reticulation of the epithelial cells and the infiltration of nonepithelial cells varied. Reticulated patches were associated with disruptions in the continuity of basement membrane, and often also with desquamation of the upper cell layers, and contained numerous small blood vessels. The epithelial cells showed considerable variation in their morphology when surrounded by infiltrating cells. The rearrangement of their cytoskeleton and redistribution of desmosomal contacts indicate the responsiveness and dynamic nature of such epithelium. Cytoplasmic glycogen granules, located in the upper strata, suggest the possibility of energy-demanding functions such as absorption and secretion. The numerous membrane-coating granules may have contributed to cell membrane thickening and possibly also to tonsillar mucosal protection. Some areas contained a few keratohyalin granules but there was little evidence of keratinisation. The presence, and sometimes the predominance, of nonepithelial cells was characteristic of the reticulated epithelium. T and B cells often infiltrated the whole epithelial thickness, and many plasma cells were located around intraepithelial vessels, while macrophages and interdigitating cells showed a patchy distribution. It is proposed that the major functions of the reticulated epithelium are: (1) to provide a favourable environment for the intimate contact between the effector cells of immune responses; (2) to facilitate direct transport of antigens; (3) to synthesise the secretory component

  17. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis.

    Directory of Open Access Journals (Sweden)

    Anders Jensen

    Full Text Available The human palatine tonsils, which belong to the central antigen handling sites of the mucosal immune system, are frequently affected by acute and recurrent infections. This study compared the microbiota of the tonsillar crypts in children and adults affected by recurrent tonsillitis with that of healthy adults and children with tonsillar hyperplasia. An in-depth 16S rRNA gene based pyrosequencing approach combined with a novel strategy that included phylogenetic analysis and detection of species-specific sequence signatures enabled identification of the major part of the microbiota to species level. A complex microbiota consisting of between 42 and 110 taxa was demonstrated in both children and adults. This included a core microbiome of 12 abundant genera found in all samples regardless of age and health status. Yet, Haemophilus influenzae, Neisseria species, and Streptococcus pneumoniae were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium necrophorum, Streptococcus intermedius and Prevotella melaninogenica/histicola were associated with recurrent tonsillitis in adults, whereas species traditionally associated with acute tonsillitis like pyogenic streptococci and Staphylococcus aureus were scarce. The findings suggest that recurrent tonsillitis is a polymicrobial infection in which interactions within consortia of taxa play an etiologic role. The study contributes to the human microbiome data, to the

  18. Residual γH2AX foci as an indication of lethal DNA lesions

    Directory of Open Access Journals (Sweden)

    Banuelos C Adriana

    2010-01-01

    Full Text Available Abstract Background Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. Methods To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. Results For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Conclusion Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.

  19. Psychometric Characteristics of the Aberrant Behavior Checklist.

    Science.gov (United States)

    Aman, Michael G.; And Others

    1985-01-01

    Information is presented on the psychometric characteristics of the Aberrant Behavior Checklist, a measure of psychotropic drug effects. Internal consistency and test-retest reliability of the checklist appeared very good. Interrater reliability was generally in the moderate range. In general, validity was established for most Aberrant Behavior…

  20. Aberration coefficients of curved holographic optical elements

    Science.gov (United States)

    Verboven, P. E.; Lagasse, P. E.

    1986-11-01

    A general formula is derived that gives all aberration terms of holographic optical elements on substrates of any shape. The spherical substrate shape and the planar substrate shape are treated as important special cases. A numerical example illustrates the need of including higher-order aberrations.

  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. Repeatability of peripheral aberrations in young emmetropes.

    Science.gov (United States)

    Baskaran, Karthikeyan; Theagarayan, Baskar; Carius, Staffan; Gustafsson, Jörgen

    2010-10-01

    The purpose of this study is to assess the intrasession repeatability of ocular aberration measurements in the peripheral visual field with a commercially available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high definition-vision research). The higher-order off-axis aberrations data in young healthy emmetropic eyes are also reported. The aberrations of the right eye of 18 emmetropes were measured using an aberrometer with an open field of view that allows peripheral measurements. Five repeated measures of ocular aberrations were obtained and assessed in steps of 10° out to ±40° in the horizontal visual field (nasal + and temporal -) and -20° in the inferior visual field. The coefficient of repeatability, coefficient of variation, and the intraclass correlation coefficient were calculated as a measure of intrasession repeatability. In all eccentric angles, the repeatability of the third- and fourth-order aberrations was better than the fifth and sixth order aberrations. The coefficient of variation was coefficient was >0.90 for the third and fourth order but reduced gradually for higher orders. There was no statistical significant difference in variance of total higher-order root mean square between on- and off-axis measurements (p > 0.05). The aberration data in this group of young emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40° in the temporal field, decreasing linearly toward negative values with increasing off-axis angle into the nasal field, whereas all other higher-order aberrations showed little or no change. The complete ophthalmic analysis system-high definition-vision research provides fast, repeatable, and valid peripheral aberration measurements and can be used efficiently to measure off-axis aberrations in the peripheral visual field.

  3. Higher-Order Aberrations in Myopic Eyes

    Directory of Open Access Journals (Sweden)

    Farid Karimian

    2010-01-01

    Full Text Available Purpose: To evaluate the correlation between refractive error and higher-order aberrations (HOAs in patients with myopic astigmatism. Methods: HOAs were measured using the Zywave II aberrometer over a 6 mm pupil. Correlations between HOAs and myopia, astigmatism, and age were analyzed. Results: One hundred and twenty-six eyes of 63 subjects with mean age of 26.4±5.9 years were studied. Mean spherical equivalent refractive error and refractive astigmatism were -4.94±1.63 D and 0.96±1.06 D, respectively. The most common higher-order aberration was primary horizontal trefoil with mean value of 0.069±0.152 μm followed by spherical aberration (-0.064±0.130 μm and primary vertical coma (-0.038±0.148 μm. As the order of aberration increased from third to fifth, its contribution to total HOA decreased: 53.9% for third order, 31.9% for fourth order, and 14.2% for fifth order aberrations. Significant correlations were observed between spherical equivalent refractive error and primary horizontal coma (R=0.231, P=0.022, and root mean square (RMS of spherical aberration (R=0.213, P=0.031; between astigmatism and RMS of total HOA (R=0.251, P=0.032, RMS of fourth order aberration (R=0.35, P<0.001, and primary horizontal coma (R=0.314, P=0.004. Spherical aberration (R=0.214, P=0.034 and secondary vertical coma (R=0.203, P=0.031 significantly increased with age. Conclusion: Primary horizontal trefoil, spherical aberration and primary vertical coma are the predominant higher-order aberrations in eyes with myopic astigmatism.

  4. 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.

  5. Analysis of the Aberration in Directly-writing Atom Lithography

    Institute of Scientific and Technical Information of China (English)

    LI Chuanwen; CAI Weiquan; WANG Yuzhu

    2000-01-01

    After deriving the approximation solution which describes the motion of neutral atoms in an optical standing wave field with large detuning, the spherical aberration and the chromatic aberration are analyzed and possible methods to reduce these aberrations are discussed.

  6. 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.

  7. Aberration correction past and present.

    Science.gov (United States)

    Hawkes, P W

    2009-09-28

    Electron lenses are extremely poor: if glass lenses were as bad, we should see as well with the naked eye as with a microscope! The demonstration by Otto Scherzer in 1936 that skillful lens design could never eliminate the spherical and chromatic aberrations of rotationally symmetric electron lenses was therefore most unwelcome and the other great electron optician of those years, Walter Glaser, never ceased striving to find a loophole in Scherzer's proof. In the wartime and early post-war years, the first proposals for correcting C(s) were made and in 1947, in a second milestone paper, Scherzer listed these and other ways of correcting lenses; soon after, Dennis Gabor invented holography for the same purpose. These approaches will be briefly summarized and the work that led to the successful implementation of quadupole-octopole and sextupole correctors in the 1990 s will be analysed. In conclusion, the elegant role of image algebra in describing image formation and processing and, above all, in developing new methods will be mentioned.

  8. On aberration in gravitational lensing

    CERN Document Server

    Sereno, M

    2008-01-01

    It is known that a relative translational motion between the deflector and the observer affects gravitational lensing. In this paper, a lens equation is obtained to describe such effects on actual lensing observables. Results can be easily interpreted in terms of aberration of light-rays. Both radial and transverse motions with relativistic velocities are considered. The lens equation is derived by first considering geodesic motion of photons in the rest-frame Schwarzschild spacetime of the lens, and, then, light-ray detection in the moving observer's frame. Due to the transverse motion images are displaced and distorted in the observer's celestial sphere, whereas the radial velocity along the line of sight causes an effective re-scaling of the lens mass. The Einstein ring is distorted to an ellipse whereas the caustics in the source plane are still point-like. Either for null transverse motion or up to linear order in velocities, the critical curve is still a circle with its radius corrected by a factor (1+z...

  9. 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

    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.

  10. Image-based EUVL aberration metrology

    Science.gov (United States)

    Fenger, Germain Louis

    A significant factor in the degradation of nanolithographic image fidelity is optical wavefront aberration. As resolution of nanolithography systems increases, effects of wavefront aberrations on aerial image become more influential. The tolerance of such aberrations is governed by the requirements of features that are being imaged, often requiring lenses that can be corrected with a high degree of accuracy and precision. Resolution of lithographic systems is driven by scaling wavelength down and numerical aperture (NA) up. However, aberrations are also affected from the changes in wavelength and NA. Reduction in wavelength or increase in NA result in greater impact of aberrations, where the latter shows a quadratic dependence. Current demands in semiconductor manufacturing are constantly pushing lithographic systems to operate at the diffraction limit; hence, prompting a need to reduce all degrading effects on image properties to achieve maximum performance. Therefore, the need for highly accurate in-situ aberration measurement and correction is paramount. In this work, an approach has been developed in which several targets including phase wheel, phase disk, phase edges, and binary structures are used to generate optical images to detect and monitor aberrations in extreme ultraviolet (EUV) lithographic systems. The benefit of using printed patterns as opposed to other techniques is that the lithography system is tested under standard operating conditions. Mathematical models in conjunction with iterative lithographic simulations are used to determine pupil phase wavefront errors and describe them as combinations of Zernike polynomials.

  11. 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.

  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. Demonstrating optical aberrations in the laboratory

    CSIR Research Space (South Africa)

    Naidoo, Darryl

    2009-07-01

    Full Text Available in the laboratory D. Naidoo1,2 , C. Mafusire1,2 and A. Forbes1,2 1 CSIR National Laser Centre 2 School of Physics, University of KwaZulu-Natal AN OPTICAL ABERRATION IS A DISTORTION OF AN IMAGE AS COMPARED TO THE OBJECT DUE TO DEFECTS IN AN OPTICAL SYSTEM TILT... COEFFICIENT ODDWEIGHTING EVEN ODD ABERRATION PHASE EVENWEIGHTING COEFFICIENT COEFFICIENT ZERNIKE POLYNOMIALS ARE FITTED TO 3-DIMENSIONAL DATA TO DESCRIBE THE ABERRATIONS OF WAVEFRONT MEASUREMENTS IMPORTANT ELEMENTS OF DESIGN INCLUDE A LENSLET ARRAY...

  14. Multinodal fifth-order optical aberrations of optical systems without rotational symmetry: the comatic aberrations.

    Science.gov (United States)

    Thompson, Kevin P

    2010-06-01

    Building on an earlier work on the nodal aberration theory of the 3rd-order aberrations [J. Opt. Soc. Am. A22, 1389 (2005)] and the first paper in this series on the nodal aberration theory of higher-order aberrations [J. Opt. Soc. Am. A26, 1090 (2009)], this paper continues the derivation and presentation of the intrinsic, characteristic, often multinodal geometry for each type/family of the 3rd- and 5th-order optical aberrations as categorized by parallel developments for rotationally symmetric optics. The first paper in this series on the higher-order terms developed the nodal properties of the spherical aberration family, including W(060), W(240M), and W(242), and for completeness 7th-order spherical aberration W(080). This second paper in the series develops and presents the intrinsic, characteristic, often multinodal properties of the family of comatic aberrations through 5th order, specifically W(151), W(331M), and W(333) [field-linear, 5th-order aperture coma; field-cubed, 3rd-order aperture coma; and field-cubed, elliptical coma (a 3rd-order in aperture 5th-order vector aberration)]. This paper will present the first derivations of trinodal aberrations by the author.

  15. 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

  16. [Study on detoxication of euphorbia pekinensis radix processed with vinegar on rat small intestinal crypt epithelial cells IEC-6].

    Science.gov (United States)

    Cao, Yu-Dan; Yan, Xiao-Jing; Zhang, Li; Ding, An-Wei

    2014-03-01

    To compare the difference of Euphorbia Pekinensis Radix before and after being processed with vinegar in the toxicity on rat small intestinal crypt epithelial cells IEC-6, and make a preliminary study on the mechanism of detoxication of Euphorbia Pekinensis Radix processed with vinegar. With rat small intestinal crypt epithelial cells IEC-6 as the study object, the MTT method was adopted to detect the effect of Euphorbia Pekinensis Radix before and after being processed with vinegar on IEC-6 cell activity. The morphology of cells were observed by the inverted microscope. The down-regulated mitochondrial apoptosis pathway of enterocytes caused by the vinegar processing was analyzed by using the high content screening. Compared with the negative control group, the proliferation inhibition experiment showed that Euphorbia Pekinensis Radix showed a relatively high intestinal cell toxicity (P IEC-6 cell membrane, so as to provide a basis for further explanation of the detoxication mechanism of Euphorbia Pekinensis Radix processed with vinegar.

  17. 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...

  18. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  19. Catadioptric aberration correction in cathode lens microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, R.M. [IBM T.J. Watson Research Center, PO Box 218, Yorktown Heights, NY 10598 (United States); Kamerlingh Onnes Laboratory, Leiden Institute of Physics, Niels Bohrweg 2, 2333 CA Leiden (Netherlands)

    2015-04-15

    In this paper I briefly review the use of electrostatic electron mirrors to correct the aberrations of the cathode lens objective lens in low energy electron microscope (LEEM) and photo electron emission microscope (PEEM) instruments. These catadioptric systems, combining electrostatic lens elements with a reflecting mirror, offer a compact solution, allowing simultaneous and independent correction of both spherical and chromatic aberrations. A comparison with catadioptric systems in light optics informs our understanding of the working principles behind aberration correction with electron mirrors, and may point the way to further improvements in the latter. With additional developments in detector technology, 1 nm spatial resolution in LEEM appears to be within reach. - Highlights: • The use of electron mirrors for aberration correction in LEEM/PEEM is reviewed. • A comparison is made with similar systems in light optics. • Conditions for 1 nm spatial resolution are discussed.

  20. Generalized pupil aberrations of optical imaging systems

    Science.gov (United States)

    Elazhary, Tamer T.

    In this dissertation fully general conditions are presented to correct linear and quadratic field dependent aberrations that do not use any symmetry. They accurately predict the change in imaging aberrations in the presence of lower order field dependent aberrations. The definitions of the image, object, and coordinate system are completely arbitrary. These conditions are derived using a differential operator on the scalar wavefront function. The relationships are verified using ray trace simulations of a number of systems with varying degrees of complexity. The math is shown to be extendable to provide full expansion of the scalar aberration function about field. These conditions are used to guide the design of imaging systems starting with only paraxial surface patches, then growing freeform surfaces that maintain the analytic conditions satisfied for each point in the pupil. Two methods are proposed for the design of axisymmetric and plane symmetric optical imaging systems. Design examples are presented as a proof of the concept.

  1. 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.

  2. A rat liver foci promotion study with 50-Hz magnetic fields.

    Science.gov (United States)

    Rannug, A; Holmberg, B; Mild, K H

    1993-08-01

    To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

  3. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  4. Formation of Subnuclear Foci Is a Unique Spatial Behavior of Mating MAPKs during Hyperosmotic Stress

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2013-02-01

    Full Text Available The assembly of signaling components and transcription factors in ordered subcellular structures is increasingly implicated as an important regulatory strategy for modulating the activity of cellular pathways. Here, we document the inducible formation of subnuclear foci formed by two mitogen-activated protein kinases (MAPKs in Saccharomyces cerevisiae upon hyperosmotic stress. Specifically, we demonstrate that activation of the hyperosmotic stress response pathway induces the mating pathway MAPK Fus3 and the filamentation pathway MAPK Kss1 to form foci in the nucleus that are organized by their shared downstream transcription factor Ste12. Foci formation of colocalized Ste12, Fus3, and Kss1 requires the kinase activity of the hyperosmotic response MAPK Hog1 and correlates with attenuated signaling in the mating pathway. Conversely, activation of the mating pathway prevents foci formation upon subsequent hyperosmotic stress. These results suggest that Hog1-mediated spatial localization of Fus3 and Ste12 into subnuclear foci could contribute to uncoupling the pheromone and osmolarity pathways, which share signaling components, under high-osmolarity conditions.

  5. Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer.

    Science.gov (United States)

    Wang, Donghai; Peregrina, Karina; Dhima, Elena; Lin, Elaine Y; Mariadason, John M; Augenlicht, Leonard H

    2011-06-21

    Nutritional and genetic risk factors for intestinal tumors are additive on mouse tumor phenotype, establishing that diet and genetic factors impact risk by distinct combinatorial mechanisms. In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice in which tumor etiology, lag, incidence, and frequency reflect >90% of intestinal cancer in Western societies, dietary-induced risk altered gene expression profiles predominantly in villus cells of the histologically normal mucosa, in contrast to targeting of crypt cells by inheritance of an Apc(1638N) allele or homozygous inactivation of p21(Waf1/cip1), and profiles induced by each risk factor were distinct at the gene or functional group level. The dietary-induced changes in villus cells encompassed ectopic expression of Paneth cell markers (a lineage normally confined to the bottom of small intestinal crypts), elevated expression of the Wnt receptor Fzd5 and of EphB2 (genes necessary for Paneth cell differentiation and localization to the crypt bottom), and increased Wnt signaling in villus cells. Ectopic elevation of these markers was also present in the colon crypts, which are also sites of sporadic tumors in the nutritional model. Elevating dietary vitamin D(3) and calcium, which prevents tumor development, abrogated these changes in the villus and colon cells. Thus, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele. This is fundamental for understanding how common sporadic tumors arise and in evaluating relative risk in the population.

  6. 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.

  7. Sensing Phase Aberrations behind Lyot Coronagraphs

    Science.gov (United States)

    Sivaramakrishnan, Anand; Soummer, Rémi; Pueyo, Laurent; Wallace, J. Kent; Shao, Michael

    2008-11-01

    Direct detection of young extrasolar planets orbiting nearby stars can be accomplished from the ground with extreme adaptive optics and coronagraphy in the near-infrared, as long as this combination can provide an image with a dynamic range of 107 after the data are processed. Slowly varying speckles due to residual phase aberrations that are not measured by the primary wave-front sensor are the primary obstacle to achieving such a dynamic range. In particular, non-common optical path aberrations occurring between the wave-front sensor and the coronagraphic occulting spot degrade performance the most. We analyze the passage of both low and high spatial frequency phase ripples, as well as low-order Zernike aberrations, through an apodized pupil Lyot coronagraph in order to demonstrate the way coronagraphic filtering affects various aberrations. We derive the coronagraphically induced cutoff frequency of the filtering and estimate coronagraphic contrast losses due to low-order Zernike aberrations: tilt, astigmatism, defocus, coma, and spherical aberration. Such slowly varying path errors can be measured behind a coronagraph and corrected by a slowly updated optical path delay precompensation or offset asserted on the wave front by the adaptive optics (AO) system. We suggest ways of measuring and correcting all but the lowest spatial frequency aberrations using Lyot plane wave-front data, in spite of the complex interaction between the coronagraph and those mid-spatial frequency aberrations that cause image plane speckles near the coronagraphic focal plane mask occulter's edge. This investigation provides guidance for next-generation coronagraphic instruments currently under construction.

  8. 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.

  9. 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.

  10. 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.

  11. Individual eye model based on wavefront aberration

    Science.gov (United States)

    Guo, Huanqing; Wang, Zhaoqi; Zhao, Qiuling; Quan, Wei; Wang, Yan

    2005-03-01

    Based on the widely used Gullstrand-Le Grand eye model, the individual human eye model has been established here, which has individual corneal data, anterior chamber depth and the eyeball depth. Furthermore, the foremost thing is that the wavefront aberration calculated from the individual eye model is equal to the eye's wavefront aberration measured with the Hartmann-shack wavefront sensor. There are four main steps to build the model. Firstly, the corneal topography instrument was used to measure the corneal surfaces and depth. And in order to input cornea into the optical model, high-order aspheric surface-Zernike Fringe Sag surface was chosen to fit the corneal surfaces. Secondly, the Hartmann-shack wavefront sensor, which can offer the Zernike polynomials to describe the wavefront aberration, was built to measure the wavefront aberration of the eye. Thirdly, the eye's axial lengths among every part were measured with A-ultrasonic technology. Then the data were input into the optical design software-ZEMAX and the crystalline lens's shapes were optimized with the aberration as the merit function. The individual eye model, which has the same wavefront aberrations with the real eye, is established.

  12. 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.

  13. The influence of x-ray contrast agents in computed tomography on the induction of dicentrics and {gamma}-H2AX foci in lymphocytes of human blood samples

    Energy Technology Data Exchange (ETDEWEB)

    Jost, G; Golfier, S; Pietsch, H; Lengsfeld, P; Voth, M [Bayer Schering Pharma AG, 13353 Berlin (Germany); Schmid, T E [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universitaet Muenchen, 81675 Munich (Germany); Eckardt-Schupp, F [Institute of Radiation Biology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg (Germany); Schmid, E [Institute for Cell Biology, Center for Integrated Protein Science, University of Munich, 80336 Muenchen (Germany)], E-mail: Ernst.Schmid@lrz.uni-muenchen.de

    2009-10-21

    The aim of this study was to investigate and quantify two biomarkers for radiation exposure (dicentrics and {gamma}-H2AX foci) in human lymphocytes after CT scans in the presence of an iodinated contrast agent. Blood samples from a healthy donor were exposed to CT scans in the absence or presence of iotrolan 300 at iodine concentrations of 5 or 50 mg ml{sup -1} blood. The samples were exposed to 0.025, 0.05, 0.1 and 1 Gy in a tissue equivalent body phantom. Chromosome aberration scoring and automated microscopic analysis of {gamma}-H2AX foci were performed in parts of the same samples. The theoretical physical dose enhancement factor (DEF) was calculated on the basis of the mass energy-absorption coefficients of iodine and blood and the photon energy spectrum of the CT tube. No significant differences in the yields of dicentrics and {gamma}-H2AX foci were observed in the absence or presence of 5 mg iodine ml{sup -1} blood up to 0.1 Gy, whereas at 1 Gy the yields were elevated for both biomarkers. At an iodine concentration of 50 mg ml{sup -1} serving as a positive control, a biological DEF of 9.5 {+-} 1.4 and 2.3 {+-} 0.5 was determined for dicentrics and {gamma}-H2AX foci, respectively. A physical DEF of 1.56 and 6.30 was calculated for 5 and 50 mg iodine ml{sup -1}, respectively. Thus, it can be concluded that in the diagnostic dose range (radiation and contrast dose), no relevant biological dose-enhancing effect could be detected, whereas a clear biological dose-enhancing effect could be found for a contrast dose well outside the diagnostic CT range for the complete radiation dose range with both methods.

  14. 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

  15. [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION].

    Science.gov (United States)

    Trankvilevsky, D V; Tsarenko, V A; Zhukov, V I

    2016-01-01

    The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare.

  16. 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

    2012-05-22

    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.

  17. 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

  18. 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

  19. SPO11-independent DNA repair foci and their role in meiotic silencing.

    Directory of Open Access Journals (Sweden)

    Fabrizia Carofiglio

    2013-06-01

    Full Text Available In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI. A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC, is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF, and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  20. SPO11-independent DNA repair foci and their role in meiotic silencing.

    Science.gov (United States)

    Carofiglio, Fabrizia; Inagaki, Akiko; de Vries, Sandra; Wassenaar, Evelyne; Schoenmakers, Sam; Vermeulen, Christie; van Cappellen, Wiggert A; Sleddens-Linkels, Esther; Grootegoed, J Anton; Te Riele, Hein P J; de Massy, Bernard; Baarends, Willy M

    2013-06-01

    In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs) are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI). A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC), is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF)), and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF) and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  1. High-resolution CT features of bleeding foci in patients with massive hemoptysis

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Keum Soo; Lee, Ki Nam; Jung, Won Jung; Kim, Jae Ic; Kang, Myong Jin; Park, Byeong Ho [Donga Univ. College of Medicine, Pusan (Korea, Republic of)

    2000-12-01

    To compare the high-resolution CT features of bleeding foci in patients with massive hemoptysis during embolization with those revealed by angiography. Between June 1997 and June 1999, we evaluated 25 patients who from among a total of 49 with arterial embolization due to massive hemoptysis underwent HRCT prior to embolization. We retrospectively analyzed medical records, and angiographic and HRCT findings. The time interval between HRCT and arterial embolization varied from two hours to six days. Angiography indicated that the bronchial, intercostal and internal mammary artery, and branches of the subclavian, were the foci of bleeding, and indicated the location of these in each pulmonary lobe. The HRCT findings were evaluated in terms of cavity, air-meniscus sign, bronchial dilatation, consolidation, ground-glass opacity, and fibrotic scar. We anlayzed the corresponding sites of HRCT and the angiographic findings of the foci of bleeding. In 24 of 25 patients, the foci of bleeding were angiographically confirmed, their presence being noted in 28 pulmonary lobes. HRCT findings corresponding to the bleeding foci revealed by angiography were the air-meniscus sign (8 of 10 lobes, 80.0%), cavity (7 of 9 lobes, 77.8%), bronchial dilatation (21 of 30 lobes, 70.0%), and fibrotic scar (1 of 23 lobes, 4.3%). The findings in areas of consolidation and/or ground-glass opacity only did not correspond, however. As compared with those revealed by angiography, the HRCT features of bleeding foci in patients with massive hemoptysis during embolization are in order of frequency, the air-meniscus sign, cavity, and bronchial dilatation.

  2. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J. M.; Span, L. F. R.; Stokman, M. A.; van Winkelhoff, A. J.; Vissink, A.; Spijkervet, F. K. L.

    2016-01-01

    Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  3. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J M; Span, L. F. R.; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  4. Repair of abnormal perfusion foci in idiopathic epilepsy patients under long-term antiepileptic treatment

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Siyu Zhao; Yaqing Liu

    2011-01-01

    Epileptic seizure control and the disappearance of epileptiform discharge are not indicative of the absence of abnormal perfusion foci.Perfusion abnormalities are a major cause of epileptic discharge, and the existence of abnormal perfusion foci implies possible relapse.Very little is known about perfusion abnormality repair in epilepsy.The present study selected 43 cases of idiopathic epilepsy under antiepileptic drug control for an average of 24 months.Comparisons between interictal single-photon emission CT (SPECT)images and long-term electroencephalogram (EEG) pre- and post-treatment showed that cases of normal SPECT increased by 48% (12/25) following treatment, with a total number of 15 reduced foci (36%, 15/41).Perfusion foci, i.e., region of interest, were altered following treatment.These changes included:normal to abnormal in 3 cases (7%, 3/43; 2 hyperperfusion and 1 hypoperfusion); abnormal to normal in 14 cases (32%, 14/43; 10 pre-treatment hypoperfusion and 4 hyperperfusion); abnormal to abnormal in 7 cases (16%, 7/43; hyperperfusion to hypoperfusion in 5 cases, hypoperfusion to hyperperfusion in 2 cases).Long-term EEG revealed in an increase in the number of normal cases by 20 (40%, 20/39), and there were 25 fewer cases with epileptiform discharges (66%, 25/38).These findings demonstrate that long-term control of anti-epileptic drugs partially repaired cerebral perfusion abnormalities and reduced epileptiform discharges in idiopathic epilepsy.

  5. Sandfly fauna of endemic leishmaniasis foci in Anzoátegui State, Venezuela.

    Science.gov (United States)

    González, R; Jorquera, A; De Sousa, L; Ledezma, E; Devera, R

    2002-01-01

    A census of the sandfly fauna was undertaken in 1993-98 in 5 endemic leishmaniasis foci situated at different altitudes in Anzoátegui State, Venezuela. From the 17 species of Lutzomyia identified, we believe that Lu. ovallesi, Lu. panamensis and Lu. gomezi are the probable vectors of cutaneous leishmaniasis, while Lu. evansi might transmit visceral leishmaniasis.

  6. Genetic micro-heterogeneity of Leishmania major in emerging foci of zoonotic cutaneous leishmaniasis in Tunisia.

    Science.gov (United States)

    Attia, Hanene; Sghaier, Rabiaa M; Gelanew, Tesfaye; Bali, Aymen; Schweynoch, Carola; Guerfali, Fatma Z; Mkannez, Ghada; Chlif, Sadok; Belhaj-Hamida, Nabil; Dellagi, Koussay; Schönian, Gabriele; Laouini, Dhafer

    2016-09-01

    Tunisia is endemic for zoonotic cutaneous leishmaniasis (ZCL), a parasitic disease caused by Leishmania (L.) major. ZCL displays a wide clinical polymorphism, with severe forms present more frequently in emerging foci where naive populations are dominant. In this study, we applied the multi-locus microsatellite typing (MLMT) using ten highly informative and discriminative markers to investigate the genetic structure of 35 Tunisian Leishmania (L.) major isolates collected from patients living in five different foci of Central Tunisia (two old and three emerging foci). Phylogenetic reconstructions based on genetic distances showed that nine of the ten tested loci were homogeneous in all isolates with homozygous alleles, whereas one locus (71AT) had a 58/64-bp bi-allelic profile with an allele linked to emerging foci. Promastigote-stage parasites with the 58-bp allele tend to be more resistant to in vitro complement lysis. These results, which stress the geographical dependence of the genetic micro-heterogeneity, may improve our understanding of the ZCL epidemiology and clinical outcome.

  7. 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.

  8. Proliferation and mRNA expression of absorptive villous cell markers and mineral transporters in prolactin-exposed IEC-6 intestinal crypt cells.

    Science.gov (United States)

    Teerapornpuntakit, Jarinthorn; Wongdee, Kannikar; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-06-01

    During pregnancy and lactation, prolactin (PRL) enhances intestinal absorption of calcium and other minerals for fetal development and milk production. Although an enhanced absorptive efficiency is believed to mainly result from the upregulation of mineral transporters in the absorptive villous cells, some other possibilities, such as PRL-enhanced crypt cell proliferation and differentiation to increase the absorptive area, have never been ruled out. Here, we investigated cell proliferation and mRNA expression of mineral absorption-related genes in the PRL-exposed IEC-6 crypt cells. As expected, the cell proliferation was not altered by PRL. Inasmuch as the mRNA expressions of villous cell markers, including dipeptidylpeptidase-4, lactase and glucose transporter-5, were not increased, PRL was not likely to enhance crypt cell differentiation into the absorptive villous cells. In contrast to the previous findings in villous cells, PRL was found to downregulate the expression of calbindin-D(9k), claudin-3 and occludin in IEC-6 crypt cells, while having no effect on transient receptor potential vanilloid family channels-5/6, plasma membrane Ca(2+)-ATPase (PMCA)-1b and Na(+)/Ca(2+) exchanger-1 expression. In conclusion, IEC-6 crypt cells did not respond to PRL by increasing proliferation or differentiation into villous cells. The present results thus supported the previous hypothesis that PRL enhanced mineral absorption predominantly by increasing transporter expression and activity in the absorptive villous cells. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Prenatal hydronephrosis caused by aberrant renal vessels

    DEFF Research Database (Denmark)

    Lenz, K; Thorup, Jørgen Mogens; Rabol, A;

    1996-01-01

    With routine use of obstetric ultrasonography, fetal low-grade hydronephrosis is commonly detected, but may resolve spontaneously after birth. Two cases are presented to illustrate that in some cases such findings can express intermittent hydronephrosis caused by aberrant renal vessels. Renal...

  10. 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.

  11. Functional Analysis and Treatment of Aberrant Behavior.

    Science.gov (United States)

    Mace, F. Charles; And Others

    1991-01-01

    This article reviews general classes of variables which help to maintain aberrant behavior including attention seeking, sensory and perceptual consequences, and access to materials or activities. Suggestions for a methodology providing a comprehensive functional analysis are offered which include descriptive analysis, hypothesis forming,…

  12. Assessing the construct validity of aberrant salience.

    Science.gov (United States)

    Schmidt, Kristin; Roiser, Jonathan P

    2009-01-01

    We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT). The "aberrant salience" measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance (LIrr), attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a LIrr task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for approximately 75% of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated "Introvertive Anhedonia" schizotypy, replicating our previous finding. LIrr loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of LIrr and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  13. [Aberrant pancreas with a double intestinal location].

    Science.gov (United States)

    Yenon, K; Lethurgie, C; Bokobza, B

    2005-01-01

    The authors report one exceptional case of aberrant pancreas with a double intestinal location (jejunum and Meckel's diverticulum) in a thirty-year-old patient. Digestive haemorrhage and the abdominal colic were the revealing clinical signs. The enteroscopy guided by the enteroscanner, was the indicated complementary investigation for the preoperative diagnosis. The research of other locations during the operation should be systematic.

  14. Optical advantages of astigmatic aberration corrected heliostats

    Science.gov (United States)

    van Rooyen, De Wet; Schöttl, Peter; Bern, Gregor; Heimsath, Anna; Nitz, Peter

    2016-05-01

    Astigmatic aberration corrected heliostats adapt their shape in dependence of the incidence angle of the sun on the heliostat. Simulations show that this optical correction leads to a higher concentration ratio at the target and thus in a decrease in required receiver aperture in particular for smaller heliostat fields.

  15. Quality factor of aberrated gaussian laser beams

    CSIR Research Space (South Africa)

    Mafusire, C

    2010-09-01

    Full Text Available A model is used to calculate the beam quality factor of a laser beam from Zernike coefficients. It is tested by programming aberration coefficients on a laser beam and measuring the beam quality using a Shack-Hartmann wavefront sensor. The two show...

  16. 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.

  17. The Aberrant Coronary Artery - The Management Approach.

    Science.gov (United States)

    King, Nina-Marie; Tian, David D; Munkholm-Larsen, Stine; Buttar, Sana N; Chow, Vincent; Yan, Tristan

    2017-07-03

    An aberrant coronary artery is a rare clinical occurrence with an incidence of 0.05-1.2%. Often it is an incidental finding detected on coronary angiography or at autopsy. However, symptomatic patients can experience angina, arrhythmia, sudden death or non-specific symptoms such as dyspnoea and syncope. At present, there are no guidelines or dedicated studies assessing the treatment of an aberrant coronary artery leaving management options for these patients controversial. Selected international cardiothoracic surgeons were surveyed electronically in November 2016 to determine whether consensus exists on different management aspects for patients with an aberrant coronary artery arising from the contralateral sinus with an interarterial course. For asymptomatic patients with either an aberrant left main coronary artery (ALMCA) arising from the contralateral sinus or an aberrant right main coronary artery (ARMCA) arising from the contralateral sinus, there was no consensus on surgical correction of the anomaly. If myocardial ischaemia was demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction was the consensus between the surveyed surgeons. If surgery was deemed appropriate, coronary artery bypass surgery utilising the internal mammary artery was marginally preferred by the respondents in patients with an ALMCA whilst unroofing of the coronary ostium was preferred in patients with an ARMCA. Although no consensus was reached, a large proportion of respondents would not treat a patient over the age of 30 years differently compared to those under 30 years old. For symptomatic patients or if myocardial ischaemia is demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction is indicated. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the

  18. Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

    Directory of Open Access Journals (Sweden)

    Aten Jacob

    2011-06-01

    Full Text Available Abstract Background Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB, chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results has reduced general application. An additional type of information is required for the increasing application of high-LET radiation in cancer therapy: the Relative Biological Effectiveness (RBE for effects in tumours and normal tissues. Relevant information on RBE values might be derived from studies on cells in culture. Methods To evaluate relationships between DNA-DSB, chromosome aberrations and the clinically most relevant effect of cell reproductive death, for ionizing radiations of different LET, dose-effect relationships were determined for the induction of these effects in cultured SW-1573 cells irradiated with gamma-rays from a Cs-137 source or with α-particles from an Am-241 source. RBE values were derived for these effects. Ionizing radiation induced foci (IRIF of DNA repair related proteins, indicative of DSB, were assessed by counting gamma-H2AX foci. Chromosome aberration frequencies were determined by scoring fragments and translocations using premature chromosome condensation. Cell survival was measured by colony formation assay. Analysis of dose-effect relations was based on the linear-quadratic model. Results Our results show that, although both investigated radiation types induce similar numbers of IRIF per absorbed dose, only a small fraction of the DSB induced by the low-LET gamma-rays result in chromosome rearrangements and cell reproductive death, while this fraction is considerably enhanced for the high-LET alpha-radiation. Calculated RBE values derived for the linear components of dose-effect relations for gamma-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0 ± 0.3, 14

  19. Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: a retrospective study of 418 cases of carcinomas.

    Science.gov (United States)

    Boros, Monica; Marian, Cristina; Moldovan, Cosmin; Stolnicu, Simona

    2012-10-15

    The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated. A retrospective study of 418 cases of breast carcinomas was conducted over a 3-year period. The histological tumor types and histological grades of multifocal/multicentric carcinomas in each tumor focus were compared, and mismatches among foci were recorded. Ninety-one of the 418 cases reviewed had multiple carcinomas (21.77%). A comparison between multiple synchronous tumor foci revealed that their histological type was different in 12.08% of the cases. Mismatches among foci were also observed in 9.89% of the cases when evaluating the histological grade, and 5 out of 9 additional tumor foci with a different grade from the largest (index) tumor (55.55%) displayed a higher grade compared to the index tumor. Since the histological tumor type and histological grade of the individual foci may vary considerably within the same tumor and the additional foci may be of higher grade than the index tumor, we believe that reporting morphologic parameters with more unfavorable characteristics in addition to the parameters of the index tumor is imperative.

  20. Role of Krüppel-like factor 5 in the maintenance of the stem cell niche in the intestinal crypt.

    Science.gov (United States)

    Kuruvilla, Jes G; Ghaleb, Amr M; Bialkowska, Agnieszka B; Nandan, Mandayam O; Yang, Vincent W

    The intestinal epithelium is a tissue that undergoes continuous self-renewal initiated at the bottom of the crypts, which harbor the intestinal stem cell (ISC) pool. The ISC pool is sub-divided into crypt base columnar (CBC) cells at the crypt bottom and label retention cells (LRC) at position +4 from the crypt bottom. CBC cells are marked by Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) while LRC cells are identified by several markers including Bmi1, mTert, Hopx, Lrig1, and Sox9. Krüppel-like factors (KLFs) belong to a family of transcription factors that exert important physiological function in various tissues. In the intestine, KLF4 is predominantly expressed in the terminally differentiated, non-proliferating cells lining the villus. Its deletion in the adult mouse intestine results in perturbed homeostasis. In contrast, KLF5 is expressed in actively proliferating cells of the intestinal crypt, including CBC cells and transit amplifying (TA) cells. We recently investigated the effect of Klf5 deletion specifically from the Lgr5-expressing CBC cells in adult mouse intestine using an inducible Cre recombinase system. Shortly (3-5 days) after Cre induction, proliferation of both CBC and TA cells ceased, which was accompanied by an increase in apoptosis in the crypt. Beginning at two weeks following Cre induction, both Klf5 expression and proliferation re-appeared but without the re-emergence of Lgr5-positive CBC cells, which were eventually depleted by four months following induction. These findings indicate that KLF5 plays an important role in regulating proliferation and survival of CBC stem cells in the intestine.

  1. Protein kinase D1 mediates stimulation of DNA synthesis and proliferation in intestinal epithelial IEC-18 cells and in mouse intestinal crypts.

    Science.gov (United States)

    Sinnett-Smith, James; Rozengurt, Nora; Kui, Robert; Huang, Carlos; Rozengurt, Enrique

    2011-01-07

    We examined whether protein kinase D1 (PKD1), the founding member of a new protein kinase family, plays a critical role in intestinal epithelial cell proliferation. Our results demonstrate that PKD1 activation is sustained, whereas that of PKD2 is transient in intestinal epithelial IEC-18 stimulated with the G(q)-coupled receptor agonists angiotensin II or vasopressin. PKD1 gene silencing utilizing small interfering RNAs dramatically reduced DNA synthesis and cell proliferation in IEC-18 cells stimulated with G(q)-coupled receptor agonists. To clarify the role of PKD1 in intestinal epithelial cell proliferation in vivo, we generated transgenic mice that express elevated PKD1 protein in the intestinal epithelium. Transgenic PKD1 exhibited constitutive catalytic activity and phosphorylation at the activation loop residues Ser(744) and Ser(748) and on the autophosphorylation site, Ser(916). To examine whether PKD1 expression stimulates intestinal cell proliferation, we determined the rate of crypt cell DNA synthesis by detection of 5-bromo-2-deoxyuridine incorporated into the nuclei of crypt cells of the ileum. Our results demonstrate a significant increase (p < 0.005) in DNA-synthesizing cells in the crypts of two independent lines of PKD1 transgenic mice as compared with non-transgenic littermates. Morphometric analysis showed a significant increase in the length and in the total number of cells per crypt in the transgenic PKD1 mice as compared with the non-transgenic littermates (p < 0.01). Thus, transgenic PKD1 signaling increases the number of cells per crypt by stimulating the rate of crypt cell proliferation. Collectively, our results indicate that PKD1 plays a role in promoting cell proliferation in intestinal epithelial cells both in vitro and in vivo.

  2. 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.

  3. 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

  4. Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon

    Directory of Open Access Journals (Sweden)

    Njiokou F.

    2010-03-01

    Full Text Available An explanation of the endemic nature and/or the resurgence of Human African Trypanosomiasis (HAT in the historic foci in West and Central Africa may be the existence of an animal reservoir. In some HAT foci, pigs were found infected by Trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. This study aims to determine the prevalence of T. b. gambiense in domestic animal species (goat, sheep, pig and dog commonly found in the four active HAT foci in Cameroon (Bipindi, Fontem, Campo and Doumé. Blood samples were collected from 307 pigs, 264 goats, 267 sheep and 37 dogs and used for parasitological (QBC, immunological (LiTat 1.3 CATT and molecular (PCR analyses. QBC detected trypanosomes in 3.88 % domestic animals while 22.7 % were sero-positive with LiTat 1.3 CATT tests. Of the 875 animals analysed, 174 (19.88 % harboured T. brucei s.l. DNA, found in each of the four types of animal and in the four localities. The infection rate significantly differed among the animal species (p < 0.0001 and localities (p < 0.0001. The PCR also revealed T. b. gambiense group 1 DNA in 27 (3.08 % domestic animals. The specific infection rates were as follows: sheep (6.74 %, goats (3.08 %, pigs (0.32 % and dogs (0 %. T. b. gambiense was found in 8 (3.92 % animals from Bipindi, 15 (4.83 % from Campo, 4 (2.59 % from Fontem-Center and none from Doumé. The infection rates significantly differed between the localities, and correlated with the intensity of HAT transmission in the foci.

  5. 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.

  6. 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.

  7. 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.

  8. Evaluation of three-dimensional distribution of foci of diffuse lung diseases with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Masamitsu [Nagoya City Univ. (Japan). Medical School

    1998-11-01

    Three-dimensional distribution of foci of diffuse lung disease was evaluated by CT image, and it was examined whether each lung disease could be diagnosed by different distribution. Subjects were 120 cases (idiopathic interstitial pneumonia 15 cases, sarcoidosis 23 cases, miliary tuberculosis 10 cases, diffuse panbronchiolitis 7 cases, chronic pulmonary emphysema 6 cases, pulmonary metastasis 9 cases, SLE 6 cases, PSS 8 cases, dermatomyositis (DM) 6 cases, RA 7 cases, SjS 9 cases and others 14 cases). CT image was obtained from apex to base of lung with 10 mm gapless. The image was divided into three parts in both head-tail direction and back-front direction, and two parts in cortex medulla direction, and the ratio of foci to whole in each part was evaluated in five phases, and the part with the highest ratio was determined as the predominant side. In idiopathic interstitial pneumonia, sarcoidosis, miliary tuberculosis, diffuse panbronchiolitis, chronic pulmonary emphysema, pulmonary metastasis, PSS and DM, the predominant side was confirmed, respectively, and usefulness of differential diagnosis was recognized. Constant distribution wasn't recognized in SLE, RA and SjS, because the state of disease was not always same in the foci of these diseases. (K.H.)

  9. 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.

  10. Enhancing effects of mustard oil on preneoplastic hepatic foci development in Wistar rats.

    Science.gov (United States)

    Shukla, Yogeshwer; Arora, Annu

    2003-02-01

    Dietary habits are known to be the major contributory factor in the development of cancer. Mustard oil, which is extensively used in India and elsewhere as a flying and cooking medium, is reported to induce an inflammatory response. The development of altered hepatic foci is an early carcinogenic change in rat liver in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. In the present study, the development of preneoplastic lesions was observed following administration of mustard oil (0.5 mL/day for 8 weeks) in DEN-initiated and partially hepatomized Wistar rats. A significant decrease in the relative and absolute liver weight of mustard oil-exposed rats was recorded. The results revealed a significant increase in the number and area of placental glutathione-S-transferase (GST-P) and gamma-glutamyl transpeptidase (GGT)-positive foci in mustard oil-administered animals. The GST-P- and GGT-positive foci were more prominent in the animals given boiled (up to 300 degrees C for 3 hours) mustard oil in comparison to the animals given fresh mustard oil. These results indicate the possible tumourigenic risk associated with mustard oil consumption.

  11. Lack of promoting activity of four pesticides on induction of preneoplastic liver cell foci in rats.

    Science.gov (United States)

    Kato, T; Ogiso, T; Kato, K; Sano, M; Hasegawa, R; Shirai, T; Ito, N

    1995-01-01

    Four pesticides were examined for hepatopromoting activity using a medium-term bioassay based upon induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gave negative results, the numbers and areas of GST-P positive foci not exceeding the control values for animals given DEN alone. Indeed, a significant reduction of foci development was seen for EPN (75 ppm). These findings provide experimental evidence that the presently examined four pesticides do not have hepatocarcinogenic potential in rats.

  12. 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...

  13. Assessing the construct validity of aberrant salience

    Directory of Open Access Journals (Sweden)

    Kristin Schmidt

    2009-12-01

    Full Text Available We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT. The “aberrant salience” measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance, attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a learned irrelevance task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for ~75% percent of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated “Introvertive Anhedonia” schizotypy, replicating our previous finding. Learned irrelevance loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of learned irrelevance and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  14. Cosmological parameter estimation: impact of CMB aberration

    CERN Document Server

    Catena, Riccardo

    2012-01-01

    The peculiar motion of an observer with respect to the CMB rest frame induces an apparent deflection of the observed CMB photons, i.e. aberration, and a shift in their frequency, i.e. Doppler effect. Both effects distort the temperature multipoles a_lm's via a mixing matrix at any l. The common lore when performing a CMB based cosmological parameter estimation is to consider that Doppler affects only the l=1 multipole, and neglect any other corrections. In this paper we reconsider the validity of this assumption, showing that it is actually not robust when sky cuts are included to model CMB foreground contaminations. Assuming a simple fiducial cosmological model with five parameters, we simulated CMB temperature maps of the sky in a WMAP-like and in a Planck-like experiment and added aberration and Doppler effects to the maps. We then analyzed with a MCMC in a Bayesian framework the maps with and without aberration and Doppler effects in order to assess the ability of reconstructing the parameters of the fidu...

  15. [Familial, structural aberration of the Y chromosome with fertility disorders].

    Science.gov (United States)

    Gall, H; Schmid, M; Schmidtke, J; Schempp, W; Weber, L

    1985-11-01

    Cytogenetic studies on a patient with Klinefelter's syndrome revealed an inherited, structural aberration of the Y-chromosome which has not been described before. The aberrant Y-chromosome was characterized by eight different banding methods. The value of individual staining techniques in studies on Y-heterochromatin aberrations is emphasized. Analysis of the cytogenetic studies (banding methods, restriction endonuclease of DNA, and measurement of the length of the Y-chromosome) permits an interpretation to be made on how the aberrant Y-chromosome originated. The functions of the Y-chromosome are discussed. The decrease in fertility (cryptozoospermia) in the two brothers with the same aberrant Y-chromosome was striking.

  16. 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

  17. Radiotherapeutical chromosomal aberrations in laryngeal cancer patients

    Directory of Open Access Journals (Sweden)

    Stošić-Divjak Svetlana L.

    2009-01-01

    Full Text Available Introduction. The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. Material and methods. The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health 'Dr Dragomir Karajovic' in Belgrade. Results. The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. Discussion.. We have consluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. Conclusion. It has been concluded that the increase of absorbed radiation dose in

  18. 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

  19. 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...

  20. Chromatic variation of aberration: the role of induced aberrations and raytrace direction

    Science.gov (United States)

    Berner, A.; Nobis, T.; Shafer, D.; Gross, H.

    2015-09-01

    The design and optimization process of an optical system contains several first order steps. The definition of the appropriate lens type and the fixation of the raytrace direction are some of them. The latter can be understood as a hidden assumption rather than an aware design step. This is usually followed by the determination of the paraxial lens layout calculated for the primary wavelength. It is obvious, that for this primary wavelength the paraxial calculations are independent of raytrace direction. Today, most of the lens designs are specified not to work only for one wavelength, but in a certain wavelength range. Considering such rays of other wavelengths, one can observe that depending on the direction there will already occur differences in the first order chromatic aberrations and additionally in the chromatic variation of the third-order aberrations. The reason for this effect are induced aberrations emerging from one surface to the following surfaces by perturbed ray heights and ray angles. It can be shown, that the total amount of surface-resolved first order chromatic aberrations and the chromatic variation of the five primary aberrations can be split into an intrinsic part and an induced part. The intrinsic part is independent of the raytrace direction whereas the induced part is not.

  1. 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.

  2. Nodal aberration theory for wild-filed asymmetric optical systems

    Science.gov (United States)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  3. Imaging Features that Discriminate between Foci Induced by High-and Low-LET Radiation in Human Fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano,Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-10-08

    In this study, we investigated the formation ofradiation-induced foci in normal human fibroblasts exposed to X rays or130 keV/mum nitrogen ions using antibodies to phosphorylated proteinkinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantifythe immunofluorescence of radiation-induced foci. The size ofradiation-induced foci increased for both proteins over a 2-h periodafter nitrogen-ion irradiation, while the size of radiation-induced focidid not change after exposure to low-LET radiation. The number ofradiation-induced ATMp foci showed a more rapid rise and greaterfrequency after X-ray exposure and was resolved more rapidly such thatthe frequency of radiation-induced foci decreased by 90 percent comparedto 60 percent after exposure to high-LET radiation 2 h after 30 cGy. Incontrast, the kinetics of radiation-induced gamma-H2AX focus formationwas similar for high- and low-LET radiation in that it reached a plateauearly and remained constant for up to 2 h. High-resolution 3D images ofradiation-induced gamma-H2AX foci and dosimetry computation suggest thatmultiple double-strand breaks from nitrogen ions are encompassed withinlarge nuclear domains of 4.4 Mbp. Our work shows that the size andfrequency of radiation-induced foci vary as a function of radiationquality, dose, time and protein target. Thus, even though double-strandbreaks and radiation-induced foci are correlated, the dynamic nature ofboth contradicts their accepted equivalence for low doses of differentradiation qualities.

  4. p53 binding protein 1 foci as a biomarker of DNA double strand breaks induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C.K.M.; Wong, M.Y.P.; Lam, R.K.K.; Ho, J.P.Y. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chiu, S.K. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2011-12-21

    Foci of p53 binding protein 1 (53 BP1) have been used as a biomarker of DNA double-strand breaks (DSBs) in cells induced by ionizing radiations. 53 BP1 was shown to relocalize into foci shortly after irradiation, with the number of foci closely paralleling the number of DNA DSBs. However, consensus on criteria in terms of the numbers of 53 BP1 foci to define cells damaged by direct irradiation or by bystander signals has not been reached, which is partly due to the presence of 53 BP1 also in normal cells. The objective of the present work was to study the changes in the distribution of cells with different numbers of 53 BP1 foci in a cell population after low-dose ionizing irradiation (<0.1 Gy) provided by alpha particles, with a view to propose feasible criteria for defining cells damaged by direct irradiation or by bystander signals. It was proposed that the change in the percentage of cells with 1-3 foci should be used for such purposes. The underlying reasons were discussed.

  5. Intraprostatic locations of tumor foci of higher grade missed by diagnostic prostate biopsy among potential candidates for active surveillance

    Science.gov (United States)

    Kim, Kwangmo; Lee, Jung Keun; Choe, Gheeyoung; Hong, Sung Kyu

    2016-01-01

    To establish optimal biopsy scheme for selection of candidates for active surveillance (AS) among prostate cancer (PCa) patients, information on topographical distribution of tumor foci of higher grade missed by contemporary biopsy amongst potential candidates of AS would certainly be useful. Thus we analyzed topographic distribution of tumor foci by examining prostatectomy specimens in 444 patients who underwent radical prostatectomy for low risk PCa. Anterior and posterior prostate areas were demarcated by a horizontal line drawn at midpoint of prostatic urethra. Among 444 subjects, patients with upgrading showed relatively higher prevalence of index tumor foci in anterior prostate than those without upgrading, though not reaching statistical significance (p = 0.252). Meanwhile, among 135 (30.4%) patients with very low risk PCa, patients with upgrading showed significantly higher prevalence of index tumor foci in anterior prostate than those without upgrading (52.2% vs 33.8%; p = 0.031). In conclusions, tumor foci of higher grade missed by diagnostic biopsy were mostly located in anterior prostate among very low risk PCa patients. Such finding would be concrete evidence to support the notion that more efforts are needed to increase accuracy in detecting tumor foci in anterior prostate among potential candidates for AS. PMID:27827421

  6. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M3 receptor-coupled calcium signals in isolated human colonic crypts

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-01-01

    Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M3 receptor subtype (CHO-M3). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC50 of 14 μM. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC50 (pKb) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M3 receptor subtype expression at the crypt-base. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC50=880 nM). In CHO-M3 cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. The present studies have demonstrated that OB inhibited M3 receptor-coupled calcium signals in human colonic crypts and CHO-M3 cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M3 receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action in IBS patients suffering with diarrhoea. PMID

  7. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M(3) receptor-coupled calcium signals in isolated human colonic crypts.

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-12-01

    1. Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. 2. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M(3) receptor subtype (CHO-M(3)). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. 3. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC(50) of 14 micro M. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC(50) (pK(b)) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). 4. Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M(3) receptor subtype expression at the crypt-base. 5. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC(50)=880 nM). 6. In CHO-M(3) cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. 7. The present studies have demonstrated that OB inhibited M(3) receptor-coupled calcium signals in human colonic crypts and CHO-M(3) cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M(3) receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action

  8. 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

  9. 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.

  10. 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.

  11. Serum and fecal canine α1-proteinase inhibitor concentrations reflect the severity of intestinal crypt abscesses and/or lacteal dilation in dogs.

    Science.gov (United States)

    Heilmann, Romy M; Parnell, Nolie K; Grützner, Niels; Mansell, Joanne; Berghoff, Nora; Schellenberg, Stefan; Reusch, Claudia E; Suchodolski, Jan S; Steiner, Jörg M

    2016-01-01

    Gastrointestinal (GI) protein loss, due to lymphangiectasia or chronic inflammation, can be challenging to diagnose. This study evaluated the diagnostic accuracy of serum and fecal canine α1-proteinase inhibitor (cα1PI) concentrations to detect crypt abscesses and/or lacteal dilation in dogs. Serum and fecal cα1PI concentrations were measured in 120 dogs undergoing GI tissue biopsies, and were compared between dogs with and without crypt abscesses/lacteal dilation. Sensitivity and specificity were calculated for dichotomous outcomes. Serial serum cα1PI concentrations were also evaluated in 12 healthy corticosteroid-treated dogs. Serum cα1PI and albumin concentrations were significantly lower in dogs with crypt abscesses and/or lacteal dilation than in those without (both P <0.001), and more severe lesions were associated with lower serum cα1PI concentrations, higher 3 days-mean fecal cα1PI concentrations, and lower serum/fecal cα1PI ratios. Serum and fecal cα1PI, and their ratios, distinguished dogs with moderate or severe GI crypt abscesses/lacteal dilation from dogs with only mild or none such lesions with moderate sensitivity (56-92%) and specificity (67-81%). Serum cα1PI concentrations increased during corticosteroid administration. We conclude that serum and fecal α1PI concentrations reflect the severity of intestinal crypt abscesses/lacteal dilation in dogs. Due to its specificity for the GI tract, measurement of fecal cα1PI appears to be superior to serum cα1PI for diagnosing GI protein loss in dogs. In addition, the serum/fecal cα1PI ratio has an improved accuracy in hypoalbuminemic dogs, but serum cα1PI concentrations should be carefully interpreted in corticosteroid-treated dogs.

  12. Histoplanimetrical study on the relationship between invasion of indigenous bacteria into intestinal crypts and proliferation of epithelial cells in rat ascending colon.

    Science.gov (United States)

    Mantani, Youhei; Takahara, Ei-Ichirou; Takeuchi, Takashi; Kawano, Junichi; Yokoyama, Toshifumi; Hoshi, Nobuhiko; Kitagawa, Hiroshi

    2013-07-31

    The relationship between the invasion of indigenous bacteria into intestinal crypts and the proliferation of epithelial cells was histoplanimetrically investigated in the rat ascending colon. Indigenous bacteria preferentially adhered to the intestinal superficial epithelial cells in the mesenterium-attached mucosa (MAM) compared to those in the mesenterium-non-attached mucosa (MNM). Intestinal crypts with indigenous bacteria were also significantly more frequently found in MAM than in MNM. Total epithelial cells, columnar epithelial cells and goblet cells were significantly more abundant in the intestinal crypts with no-indigenous bacteria in MAM (MAM-C) than those in MNM (MNM-C), whereas the columnar epithelial cells were less abundant in MAM-C than in the intestinal crypts with indigenous bacteria in MAM (MAM-C-B). Columnar epithelial cells and goblet cells immuno-positive for proliferating cell nuclear antigen (PCNA) in MAM-C were more abundant than those in MNM-C, but less abundant than those in MAM-C-B. Toll-like receptor (TLR)-2, -4 and -9 were immuno-positive in the striated borders of the intestinal superficial epithelial cells, but their positive intensities were weaker in MAM than in MNM. From these findings, indigenous bacteria were confirmed to preferentially settle on the intestinal superficial epithelium of MAM in the rat ascending colon, and low TLRs-expression might contribute to the preferential settlement of indigenous bacteria in MAM. The increase of proliferating epithelial cells is probably induced by the invasion of indigenous bacteria into the intestinal crypts of MAM.

  13. 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.

  14. Chromosomal aberrations in ISS crew members

    Science.gov (United States)

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  15. 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.

  16. Aberrations in Fresnel Lenses and Mirrors

    Science.gov (United States)

    Gregory, Don

    1999-01-01

    The NASA/MSFC Shooting Star program revealed a number of technical problems that must be solved before solar thermal propulsion can become a reality. The fundamental problem of interest here is the collection of solar energy. This is the first step in the propulsion process and indeed the most important. Everything else depends on the efficiency and focusing ability of the collection lens or mirror. An initial model of Fresnel lens behavior using a wave optics approach has been completed and the results were encouraging enough to warrant an experimental investigation. This experimental investigation confirmed some of the effects predicted and produced invaluable photographic evidence of coherence based diffraction and aberration.

  17. Mapping and assessment of epileptogenic foci using frequency-entropy templates

    Science.gov (United States)

    Ben-Jacob, Eshel; Doron, Itai; Gazit, Tomer; Rephaeli, Eden; Sagher, Oren; Towle, Vernon L.

    2007-11-01

    Much effort has been devoted to developing analysis methods of subdural electroencephalogram and depth electrode recordings of epileptic patients being evaluated for surgical resection. The general approach is to investigate the brain activity at different locations as recorded by the different electrodes in an attempt to localize the epileptogenic focus or foci. Currently, most of the methods are based on the notion that epileptogenic brain activity is associated with changes in synchronization and in complexity. Here we present a method that is based on the temporal dynamics combined with the spectral distribution of energy in terms of frequency-entropy (FE) templates. The FE templates are based upon maximum information partitioning into a set of frequency bands. The FE template is calculated by wavelet packet decomposition followed by an application of the best basis algorithm minimizing the entropy cost function. A comparison between two FE templates is performed by a special quantitative similarity measure according to the overlap in the partitioning into frequency bands and weighted by the bands’ entropy. For localization of the epileptogenic foci, the templates of each electrode during the interictal period are compared with a representative template evaluated from the ensemble of all electrodes during the ictal period. We suggest associating the locations that reveal high template similarity to the ictal template with the epileptogenic foci. To test the method and the underlying assumptions, we perform retrospective analysis of the recorded brain activity, from both grid and depth electrodes, from 11 patients suffering from medically intractable epilepsy. Application of the ictal-interictal FE template similarity analysis revealed regions in the epileptic brain in which the interictal characteristics are highly similar to those of the ictal period. To asses the foci we compared the interictal templates of the different electrodes to each other, forming

  18. 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

    phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance...... 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....

  19. 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 emp...... of the interrelationship between (a) the types and foci of commitment and (b) bidirectional knowledge sharing.......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...

  20. 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

  1. Aberration measurement from specific photolithographic images: a different approach.

    Science.gov (United States)

    Nomura, H; Tawarayama, K; Kohno, T

    2000-03-01

    Techniques for measurement of higher-order aberrations of a projection optical system in photolithographic exposure tools have been established. Even-type and odd-type aberrations are independently obtained from printed grating patterns on a wafer by three-beam interference under highly coherent illumination. Even-type aberrations, i.e., spherical aberration and astigmatism, are derived from the best focus positions of vertical, horizontal, and oblique grating patterns by an optical microscope. Odd-type aberrations, i.e., coma and three-foil, are obtained by detection of relative shifts of a fine grating pattern to a large pattern by an overlay inspection tool. Quantitative diagnosis of lens aberrations with a krypton fluoride (KrF) excimer laser scanner is demonstrated.

  2. Schistosomiasis mansoni in areas of low transmission: epidemiological characterization of Venezuelan foci

    Directory of Open Access Journals (Sweden)

    Alarcón de Noya B

    2002-01-01

    Full Text Available Severe schistosomiasis is a rare event in Venezuela nowadays, after a successful national campaign by the Schistosomiasis Control Program. Unfortunately, this program has practically disappeared, and snail surveillance in field is not a priority, anymore. Thus, schistosomiasis has become a neglected disease in this country. However, surveys in different populations from the endemic area have shown particular epidemiological features described herein. In five communities we evaluated 2,175 persons and searched for the presence of Biomphalaria glabrata snails. Some markers were used for classifying schistosomiasis foci: mean age of the persons with Schistosoma mansoni eggs in the stools, serological tests, presence of B. glabrata snails, and intensity of infection. Places without B. glabrata snails and with few schistosomiasis cases were defined as "past transmission sites"; a site with abundant snails but few cases was defined as "potential risk"; "new transmission" foci were characterized by the presence of infected snails and young people passing eggs in the stools. A "re-emergent" focus has shared these last features, showing in addition a place where schistosomiasis had been reported before. Recent evidences of active transmission with the increasing dispersion of B. glabrata snails, point out the necessity for the re-establishment of the Schistosomiasis Control Program in Venezuela.

  3. The Performance of Ictal Brain SPECT for Localizing Epileptogenic Foci in Temporal Lobe epilepsies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Sil; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Chang, Kee Hyun; Lee, Sang Kun; Chung, Chun Kee [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    Anterior temporal lobectomy has become a widely used respective surgery in patients with medically intractable temporal lobe epilepsies. Prerequisites of this resection include the accurate localization of the epileptogenic focus and the determination that the proposed resection would not result in unacceptable postoperative memory or language deficits. The purpose of this study was to evaluate the performance of ictal SPECT compared to MRI findings for localization of epileptogenic foci in this group of patients. 11 patients who had been anterior temporal oral lobectomy were evaluated with ictal {sup 99m}Tc-HMPAO SPECT and MRI. MRI showed 8/11(73%) concordant lesion to the side of surgery and ictal SPECT also showed 8/11(73%) concordant hyperperfusion. In 3 cases with incorrect or nonlocalizing findings of MRI, ictal SPECT showed concordant hyperperfusion. In 2 cases confirmed by pre-resectional invasive EEG, MRI showed bilateral and contralateral lesion but ictal SPECT showed concordant hyperperfusion. 3 delayed injection of ictal SPECT showed discordant hyperperfusion. Thus, ictal SPECT was a useful method for localizing epileptogenic foci in temporal lobe epilepsies and appeared complementay to MRI.

  4. 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)

  5. Controllable design of super-oscillatory lenses with multiple sub-diffraction-limit foci.

    Science.gov (United States)

    Li, Muyuan; Li, Wenli; Li, Haoyong; Zhu, Yechuan; Yu, Yiting

    2017-05-02

    The conventional multifocal optical elements cannot precisely control the focal number, spot size, as well as the energy distribution in between. Here, the binary amplitude-type super-oscillatory lens (SOL) is utilized, and a robust and universal optimization method based on the vectorial angular spectrum (VAS) theory and the genetic algorithm (GA) is proposed, aiming to achieve the required focusing performance with arbitrary number of foci in preset energy distribution. Several typical designs of multifocal SOLs are demonstrated. Verified by the finite-difference time-domain (FDTD) numerical simulation, the designed multifocal SOLs agree well with the specific requirements. Moreover, the full-width at half-maximum (FWHM) of the achieved focal spots is close to λ/3 for all the cases (λ being the operating wavelength), which successfully breaks the diffraction limit. In addition, the designed SOLs are partially insensitive to the incident polarization state, functioning very well for both the linear polarization and circular polarization. The optimization method presented provides a useful design strategy for realizing a multiple sub-diffraction-limit foci field of SOLs. This research can find its potentials in such fields as parallel particle trapping and high-resolution microscopy imaging.

  6. An improved classification of foci for carcinogenicity testing by statistical descriptors.

    Science.gov (United States)

    Callegaro, Giulia; Stefanini, Federico Mattia; Colacci, Annamaria; Vaccari, Monica; Urani, Chiara

    2015-10-01

    Carcinogenesis is a multi-step process involving genetic alterations and non-genotoxic mechanisms. The in vitro cell transformation assay (CTA) is a promising tool for both genotoxic and non-genotoxic carcinogenesis. CTA relies on the ability of cells (e.g. BALB/c 3T3 mouse embryo fibroblasts) to develop a transformed phenotype after the treatment with suspected carcinogens. The classification of the transformed phenotype is based on coded morphological features, which are scored under a light microscope by trained experts. This procedure is time-consuming and somewhat prone to subjectivity. Herewith we provide a promising approach based on image analysis to support the scoring of malignant foci in BALB/c 3T3 CTA. The image analysis system is a quantitative approach, based on measuring features of malignant foci: dimension, multilayered growth, and invasivity into the surrounding monolayer of non-transformed cells. A logistic regression model was developed to estimate the probability for each focus to be transformed as a function of three statistical image descriptors. The estimated sensitivity of the derived classifier (untransformed against Type III) was 0.9, with an Area Under the Curve (AUC) value equal to 0.90 under the Receiver Operating Characteristics (ROC) curve.

  7. Correcting Aberrations in Complex Magnet Systems for Muon Cooling Channels

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Maloney, B. Erdelyi, A. Afanaciev, R.P. Johnson, Y.S. Derbenev, V.S. Morozov

    2011-03-01

    Designing and simulating complex magnet systems needed for cooling channels in both neutrino factories and muon colliders requires innovative techniques to correct for both chromatic and spherical aberrations. Optimizing complex systems, such as helical magnets for example, is also difficult but essential. By using COSY INFINITY, a differential algebra based code, the transfer and aberration maps can be examined to discover what critical terms have the greatest influence on these aberrations.

  8. 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

  9. Calibration and removal of lateral chromatic aberration in images

    OpenAIRE

    Mallon, John; Whelan, Paul F.

    2007-01-01

    This paper addresses the problem of compensating for lateral chromatic aberration in digital images through colour plane realignment. Two main contributions are made: the derivation of a model for lateral chromatic aberration in images, and the subsequent calibration of this model from a single view of a chess pattern. These advances lead to a practical and accurate alternative for the compensation of lateral chromatic aberrations. Experimental results validate the proposed models and calibra...

  10. Diet induced obesity increases the risk of colonic tumorigenesis in mice.

    Science.gov (United States)

    Sikalidis, Angelos K; Fitch, Mark D; Fleming, Sharon E

    2013-10-01

    A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.

  11. 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.

  12. 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.

  13. 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

    2011-05-01

    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 7 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 7 vivax and T congolense "forest type" in Bipindi and Fontem-Center indicate their intense transmission in these foci.

  14. 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.)

  15. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  16. Aberrant angiogenesis: The gateway to diabetic complications

    Directory of Open Access Journals (Sweden)

    Sunil K Kota

    2012-01-01

    Full Text Available Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

  17. Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes

    Directory of Open Access Journals (Sweden)

    Delorenzi Mauro

    2005-05-01

    Full Text Available Abstract Background The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. Results We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8, the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff ≤ 0.05 of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p ≤ 0.05 along the anterior-posterior axis was observed. Conclusion All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the

  18. γH2AX Foci Form Preferentially in Euchromatin after Ionising-Radiation

    Science.gov (United States)

    Cowell, Ian G.; Sunter, Nicola J.; Singh, Prim B.; Austin, Caroline A.; Durkacz, Barbara W.; Tilby, Michael J.

    2007-01-01

    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 γH2AX 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 γH2AX 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 discus a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since γH2AX 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 differential responses of

  19. 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

  20. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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

  1. Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence.

    Science.gov (United States)

    Willitzki, Annika; Lorenz, Sebastian; Hiemann, Rico; Guttek, Karina; Goihl, Alexander; Hartig, Roland; Conrad, Karsten; Feist, Eugen; Sack, Ulrich; Schierack, Peter; Heiserich, Lisa; Eberle, Caroline; Peters, Vanessa; Roggenbuck, Dirk; Reinhold, Dirk

    2013-11-01

    Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double-strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose- and time-dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose-dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 μM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage.

  2. Effect of chromatic aberration on atomic-resolved spherical aberration corrected STEM images.

    Science.gov (United States)

    Kuramochi, Koji; Yamazaki, Takashi; Kotaka, Yasutoshi; Ohtsuka, Masahiro; Hashimoto, Iwao; Watanabe, Kazuto

    2009-12-01

    The effect of the chromatic aberration (C(c)) coefficient in a spherical aberration (C(s))- corrected electromagnetic lens on high-resolution high-angle annular dark field (HAADF) scanning transmission electron microscope (STEM) images is explored in detail. A new method for precise determination of the C(c) coefficient is demonstrated, requiring measurement of an atomic-resolution one-frame through-focal HAADF STEM image. This method is robust with respect to instrumental drift, sample thickness, all lens parameters except C(c), and experimental noise. It is also demonstrated that semi-quantitative structural analysis on the nanometer scale can be achieved by comparing experimental C(s)- corrected HAADF STEM images with their corresponding simulated images when the effects of the C(c) coefficient and spatial incoherence are included.

  3. In naming the dead: Autosomal and Y-chromosomal STR typing on human skeletal remains from an 18th/19th century aristocratic crypt in Gallspach, Upper Austria.

    Science.gov (United States)

    Schwarz, Reinhard; Renhart, Silvia; Gruber, Heinz; Kli Mesch, Wolfgang; Neuhuber, Franz; Cemper-Kiesslich, Jan

    2015-01-01

    Ancient DNA analyses have shown to be a powerful tool in the joint transdisciplinary assessment of archaeological records involving human remains. In this study we set out to identify single inhumations by synoptically evaluating the historical, archaeological, anthropological and molecular records on human remains from the crypt of the aristocratic family of Hoheneck (or: Hohenegg) dating to the 18(th) and 19(th) century AD. A total of 11 individuals were under investigation, yielding complete autosomal and Y-chromosomal STR profiles for 5 persons clearly showing a family group. DNA results, anthropological data and archaeological records taken together resulted in (almost) unambiguous correlation to historical records on the persons entombed in the crypt.

  4. Design of an aberration corrected low-voltage SEM

    NARCIS (Netherlands)

    Aken, R.H. van; Maas, D.J.; Hagen, C.W.; Barth, J.E.; Kruit, P.

    2010-01-01

    The low-voltage foil corrector is a novel type of foil aberration corrector that can correct for both the spherical and chromatic aberration simultaneously. In order to give a realistic example of the capabilities of this corrector, a design for a low-voltage scanning electron microscope with the lo

  5. Adaptive aberration correction using a triode hyperbolic electron mirror.

    Science.gov (United States)

    Fitzgerald, J P S; Word, R C; Könenkamp, R

    2011-01-01

    A converging electron mirror can be used to compensate spherical and chromatic aberrations in an electron microscope. This paper presents an analytical solution to a novel triode (three electrode) hyperbolic mirror as an improvement to the well-known diode (two electrode) hyperbolic mirror for aberration correction. A weakness of the diode mirror is a lack of flexibility in changing the chromatic and spherical aberration coefficients independently without changes in the mirror geometry. In order to remove this limitation, a third electrode can be added. We calculate the optical properties of the resulting triode mirror analytically on the basis of a simple model field distribution. We present the optical properties-the object/image distance, z(0), and the coefficients of spherical and chromatic aberration, C(s) and C(c), of both mirror types from an analysis of electron trajectories in the mirror field. From this analysis, we demonstrate that while the properties of both designs are similar, the additional parameters in the triode mirror improve the range of aberration that can be corrected. The triode mirror is also able to provide a dynamic adjustment range of chromatic aberration for fixed spherical aberration and focal length, or any permutation of these three parameters. While the dynamic range depends on the values of aberration correction needed, a nominal 10% tuning range is possible for most configurations accompanied by less than 1% change in the other two properties.

  6. Investigation of spherical aberration effects on coherent lidar performance

    DEFF Research Database (Denmark)

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

    2013-01-01

    In this paper we demonstrate experimentally the performance of a monostatic coherent lidar system under the influence of phase aberrations, especially the typically predominant spherical aberration (SA). The performance is evaluated by probing the spatial weighting function of the lidar system...

  7. 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...

  8. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    S K Tripathy; S Ananda Rao

    2003-01-01

    Expressions for third-order aberration in the reconstructed wave front of point objects are established by Meier. But Smith, Neil Mohon, Sweatt independently reported that their results differ from that of Meier. We found that coefficients for spherical aberration, astigmatism, tally with Meier’s while coefficients for distortion and coma differ.

  9. MAPCLASS a code to optimize high order aberrations

    CERN Document Server

    Tomás, R

    2006-01-01

    MAPCLASS is a code written in PYTHON conceived to optimize the non-linear aberrations of the Final Focus System of CLIC. MAPCLASS calls MADX-PTC to obtain the map coefficients and uses optimization algorithms like the Simplex to compensate the high order aberrations.

  10. Pattern of chromosomal aberrations in patients from north East iran.

    Science.gov (United States)

    Ghazaey, Saeedeh; Mirzaei, Farzaneh; Ahadian, Mitra; Keifi, Fatemeh; Semiramis, Tootian; Abbaszadegan, Mohammad Reza

    2013-01-01

    Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques. In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities. The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS) was the most prevalent autosomal aberration in the patients (77.1%). Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA). Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner's syndrome and 33.5% had Klinefelter's syndrome. According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  11. 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.

  12. Demonstration lessons in mathematics education: teachers' observation foci and intended changes in practice

    Science.gov (United States)

    Clarke, Doug; Roche, Anne; Wilkie, Karina; Wright, Vince; Brown, Jill; Downton, Ann; Horne, Marj; Knight, Rose; McDonough, Andrea; Sexton, Matthew; Worrall, Chris

    2013-06-01

    As part of a teacher professional learning project in mathematics education, university mathematics educators taught demonstration lessons in project primary schools. These lessons were part of a "pre-brief, teaching, and debrief" process, in which up to eight teachers observed each lesson. Using brief questionnaires completed in advance of the lesson, during the lesson, following the debrief, and several weeks later, data were collected on teachers' intended and actual observation foci and any anticipated changes in their beliefs and practices arising from the experience. There were several common themes in teachers' intended observations, including a focus on questioning, catering for individual differences, and building student engagement. As evident in other research, teachers' intended and actual observations gave greater attention to teacher actions and decision making than to student learning and thinking. In this paper, we situate demonstration lessons within teacher professional learning models, describe the features of our model, summarise teacher data, and discuss issues arising from our work.

  13. 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.

  14. 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.

  15. Differential gene expression in CD45 cells at para-aortic foci stage of chicken haematopoiesis.

    Science.gov (United States)

    Säynäjäkangas, R; Uchida, T; Vainio, O

    2009-09-01

    Para-aortic foci of chicken embryos at 6-7 days of development are considered to provide a microenvironment for haematopoietic stem cell proliferation and initial differentiation similar to that of fetal liver in mammals. Here, we have investigated the genes involved in this process by constructing and analysing a subtractive cDNA library from CD45(+) cells in para-aortic region. Among 394 analysed clones 99 distinct genes were identified by sequence homology search. Classification of the identified genes according to biological processes revealed that innate immunity-related genes are highly expressed at this stage. This can be explained by the presence of yolk sac-derived macrophages in the original tissue sample but also by the indiscriminate expression of multiple lineage-specific genes in haematopoietic stem cells and primitive progenitors. Differentially expressed genes related to transcription, signalling and lymphocyte functions are potential candidates involved in lineage commitment.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Georgescu, Walter; Tang, Jonathan; Costes, Sylvain V.

    2013-09-03

    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.

  17. 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.

  18. Creation of multiple on-axis foci and ultra-long focal depth for SPPs.

    Science.gov (United States)

    Wang, Jiayuan; Chen, Cuiyun; Sun, Zhijun

    2017-01-23

    We present the design of a plasmonic lens (PL) which is composed of pixelated nano-grooves on a gold film for the coupling and focusing of surface plasmon polaritons (SPPs) into multiple focal spots on the optical axis. The pixelated grooves are arranged along the y-axis and the x-position of each groove is optimized by the simulated annealing algorithm. PLs that implement two and three on-axis foci are presented and the designed structures have been validated with FDTD simulations. We also successfully constructed a long-focal-depth PL with a longitudinal FWHM of the focus that reached 25 plasmonic wavelengths, while its transverse field profile is maintained over 15 µm distance. The presented design method constitutes a new basis for plasmonic beam engineering, and the proposed particular SPP focal fields have potential applications in multiple imaging, particle manipulating, and plasmonic on-chip signal transmission.

  19. 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.

  20. Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo

    Institute of Scientific and Technical Information of China (English)

    Ying-Fang Fan; Zong-Hai Huang

    2002-01-01

    AIM: To study the effect of angiogenesis inhibitor TNP-470on peritoneal dissemination of colon cancer in nude mice,METHODS: The MTT assay was used to evaluate theinhibitory effect of TNP-470 on human colon cancer cell lineLovo. Lovo cells were injected into the peritoneal cavity ofBABL/C nu/nu mice and the models of peritonealdissemination were developed. Thirty nude mice wererandomly divided into control and TNP-470-treated group.In TNP-470-treated group, TNP-470 was injectedsubcutaneously every other day from day 1 until sacrifice ordeath (30 mg.kg-1). The control group received a shaminjection of the same volume saline solutionRESULTS: In vltro, TNP-470 inhibited the growth of Lovocells, with its IC50 at 2.14x102μg.L-1 In vivo, TNP-470demonstrated growth inhibition of tumors. Mice body weightand abdominal circumferences were significantly differentbetween TNP-470-treated group (24.5±3.2 g, 7.0±1.1 cm)and control group (29.5±2.1 g, 10.3±1.5 cm), P=0.005 andP=0.001. The number of disseminated foci was significantlydifferent between the control group (92.1±20.6) and theTNP-470-treated group (40.3±12.3), P<0.001. The maximalsize of foci was significantly smaller in TNP-470-treated group(3.3±0.7 mm) than that of control (7.3±2.3 mm), P=0.004.Mean survival time was significantly longer in TNP-470-treated group(98.00±12.06 d) than that in control group(41.86±9.51 d), P<0.001.CONCLUSION: Angiogenesis inhibitor TNP-470 might beeffective in treating peritoneal dissemination of colon cancerand improve the survival rate of nude mice.

  1. 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.

  2. Effects of aberrations in spatiotemporal focusing of ultrashort laser pulses.

    Science.gov (United States)

    Sun, Bangshan; Salter, Patrick S; Booth, Martin J

    2014-04-01

    Spatiotemporal focusing, or simultaneous spatial and temporal focusing (SSTF), has already been adopted for various applications in microscopy, photoactivation for biological studies, and laser fabrication. We investigate the effects of aberrations on focus formation in SSTF, in particular, the effects of phase aberrations related to low-order Zernike modes and a refractive index mismatch between the immersion medium and sample. By considering a line focus, we are able to draw direct comparison between the performance of SSTF and conventional spatial focusing (SF). Wide-field SSTF is also investigated and is found to be much more robust to aberrations than either line SSTF or SF. These results show the sensitivity of certain focusing methods to specific aberrations, and can inform on the necessity and benefit of aberration correction.

  3. 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 ...... pesticide exposure. In general, the findings indicate the importance of personal protection, during high-exposure re-entry activities, in preventing pesticide uptake and genetic damage.......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...... 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...

  4. Onset of transcription of the aminopeptidase N (leukemia antigen CD 13) gene at the crypt/villus transition zone during rabbit enterocyte differentiation

    DEFF Research Database (Denmark)

    Norén, O; Dabelsteen, E; Høyer, P E

    1989-01-01

    The sequence of a cDNA clone (2.82 kbp) of rabbit intestinal aminopeptidase N (CD 13) is reported. Using the corresponding anti-sense RNA probe, the distribution of aminopeptidase N mRNA along the crypt/villus axis of the rabbit small intestine was studied by in situ hybridization. The aminopepti......The sequence of a cDNA clone (2.82 kbp) of rabbit intestinal aminopeptidase N (CD 13) is reported. Using the corresponding anti-sense RNA probe, the distribution of aminopeptidase N mRNA along the crypt/villus axis of the rabbit small intestine was studied by in situ hybridization....... The aminopeptidase N gene is expressed along the whole length of the villus with a maximum at its base. Expression was not detected in the crypt cells. The distribution of aminopeptidase N mRNA correlates with the presence of active enzyme as monitored by histochemical staining. The results are compatible with onset...

  5. Prostaglandin-induced radioprotection of murine intestinal crypts and villi by a PGE diene analog (SC-44932) and a PGI analog (Iloprost)

    Science.gov (United States)

    Hanson, Wayne R.; Collins, Paul W.

    The aminothiols exemplified by WR-2721 are effective radioprotectors; however, their toxicity associated with hypotension, nausea, and emesis has limited their development for applications in medicine or in hazardous radiation environments. There is a need for new radioprotectors that have fewer toxic side effects when given alone or combined with reduced amounts of thiols. A variety of prostaglandins (PGs) have been shown to be radioprotective agents and some appear to have fewer toxic side effects than the aminothiols. Iloprost, a stable PGI, analog protects the clonogenic epithelial cells of intestinal crypts but does not protect epithelial cells of the villi. In contrast, an E-series omega chain diene analog designated SC-44932 protects epithelial cells of both crypts and villi. When the two are combined, protection of the crypts is additive and the villi are protected to the same degree as when SC-44932 is given alone. Since radioprotection for some PGs has been shown to be dependent upon receptors, we suggest that the pattern of radioprotection seen with these two analogs depend on the location of the respective receptors or on the ability of differentiated villus cells to respond to PGs. By studying different analogs, we hope to identify mechanisms associated with PG-induced radioprotection and to identify the most protective PG analogs for applications of radioprotection.

  6. Age-related changes in ocular aberrations with accommodation.

    Science.gov (United States)

    Radhakrishnan, Hema; Charman, W Neil

    2007-05-30

    This study investigates the changes in aberrations with monocular accommodation as a function of age. Second-order and higher order wavefront aberrations and pupil size were measured as a function of accommodation demand over the range of 0-4 D in the right eyes of 47 normal subjects with ages between 17 and 56 years. Higher order ocular Zernike aberrations were analyzed for the natural pupil size in terms of their equivalent defocus and were also determined for fixed pupil diameters of 4.5 mm in the unaccommodated eyes and 2.5 mm in the accommodating eyes. With relaxed accommodation (0 D accommodation stimulus), the major change with age was in the value of C4(0), which increased in positive value over the age range studied, although the total higher order RMS wavefront aberration did not increase. When the data were analyzed for natural pupils, spherical aberration was again found to change systematically in the positive direction with age. The equivalent defocus of total higher order RMS error for natural pupils showed no significant correlation with age (p > .05). With active accommodation, spherical aberration was found to decrease and become negative as the accommodative response increased in the younger subjects (40 years), the spherical aberration showed only small changes, some of which were positive, within the limited amplitude of accommodation available. Other higher order aberrations and the RMS of higher order aberrations did not appear to change systematically with accommodation, except in the oldest subjects. The change with age in the relationship between aberration and accommodation is interpreted in terms of the changing gradients of refractive index and surface curvatures of the crystalline lens.

  7. Epigenetic aberrations and therapeutic implications in gliomas.

    Science.gov (United States)

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  8. Aberrant DNA methylation in cloned ovine embryos

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; HOU Jian; LEI TingHua; BAI JiaHua; GUAN Hong; AN XiaoRong

    2008-01-01

    By using the approach of immunofluorescence staining with an antibody against 5-methylcytosine (5MeC), the present study detected the DNA methylation patterns of cloned ovine embryos. The em-bryos derived from in vitro fertilization were also examined for reference purpose. The results showed that: (1) during the pre-implantation development, cloned embryos displayed a similar demethylation profile to the fertilized embryos; that is, the methylation level decreased to the lowest at 8-cell stage, and then increased again at morulae stage. However, methylation level was obviously higher in cloned embryos than in stage-matched fertilized embryos, especially at 8-cell stage and afterwards; (2) at blastocyst stage, the methylation pattern in cloned embryos was different from that in fertilized em-bryos. In cloned blastocyst, inner cell mass (ICM) exhibited a comparable level to trophectoderm cells (TE), while in in-vitro fertilized blastocyst the methylation level of ICM was lower than that of TE, which is not consistent with that reported by other authors. These results indicate that DNA methylation is abnormally reprogrammed in cloned embryos, implying that aberrant DNA methylation reprogramming may be one of the factors causing cloned embryos developmental failure.

  9. 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.

  10. 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...

  11. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.

    Science.gov (United States)

    Lee, Youn-Bok; Chen, Han-Jou; Peres, João N; Gomez-Deza, Jorge; Attig, Jan; Stalekar, Maja; Troakes, Claire; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline; Adachi, Yoshitsugu; Sardone, Valentina; Miller, Jack W; Smith, Bradley N; Gallo, Jean-Marc; Ule, Jernej; Hirth, Frank; Rogelj, Boris; Houart, Corinne; Shaw, Christopher E

    2013-12-12

    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.

  12. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  13. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  14. 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.

  15. Nanoproteomic analysis of extracellular receptor kinase-1/2 post-translational activation in microdissected human hyperplastic colon lesions

    OpenAIRE

    2013-01-01

    Oncogenic activation resulting in hyperproliferative lesions within the colonic mucosa has been identified in putative precancerous lesions, aberrant crypt foci (ACF). KRAS and BRAF mutation status was determined in 172 ACF identified in the colorectum of screening subjects by in situ high-definition, magnifying chromoendoscopy. Lesions were stratified according to histology (serrated vs. distended) as previously described [1]. Due to their limiting size, however, it was not technically feasi...

  16. Omega-3 fatty acids reduce the development of preneoplasic lesions

    OpenAIRE

    Henriques,Viviana Teixeira; Dias,Cristina Maria Ganns Chaves; Sylvia do Carmo Castro FRANCESCHINI; Sabarense,Céphora Maria; Neuza Maria Brunoro COSTA; Leite,Jacqueline Isaura Alvarez; Peluzio,Maria do Carmo Gouveia

    2009-01-01

    OBJECTIVE: The purpose of this study was to evaluate the anticancer potential of dietary omega-3 supplementation to reduce induced intestinal preneoplastic lesions in Wistar rats. METHODS: A total of 58 11-week-old male Wistar rats (Rattus norvergicus, albinus variety, Rodentia) were distributed into two groups: a control group (n=25) and an omega-3-treated group (n=28). Aberrant crypt foci were induced by 1,2-dimethylhydrazine. Tissue incorporation of the supplemented omega-3 fatty acids was...

  17. Omega-3 fatty acids reduce the development of preneoplasic lesions Ácidos graxos ômega-3 reduzem o desenvolvimento de lesões pré-neoplásicas

    OpenAIRE

    Viviana Teixeira Henriques; Cristina Maria Ganns Chaves Dias; Sylvia do Carmo Castro Franceschini; Céphora Maria Sabarense; Neuza Maria Brunoro Costa; Jacqueline Isaura Alvarez Leite; Maria do Carmo Gouveia Peluzio

    2009-01-01

    OBJECTIVE: The purpose of this study was to evaluate the anticancer potential of dietary omega-3 supplementation to reduce induced intestinal preneoplastic lesions in Wistar rats. METHODS: A total of 58 11-week-old male Wistar rats (Rattus norvergicus, albinus variety, Rodentia) were distributed into two groups: a control group (n=25) and an omega-3-treated group (n=28). Aberrant crypt foci were induced by 1,2-dimethylhydrazine. Tissue incorporation of the supplemented omega-3 fatty acids was...

  18. Study of residual aberration for non-imaging focusing heliostat

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.T.; Chong, K.K.; Lim, B.H.; Lim, C.S. [Institute of Energy and Environment, Malaysia University of Science and Technology, No. 17, Jalan SS7/26, Kelana Jaya, 47301 Petaling Jaya, Selangor (Malaysia)

    2003-08-01

    Instead of using a specific focusing geometry, a non-imaging focusing heliostat has no fixed geometry but is composed of many small movable element mirrors that can be manoeuvred to eliminate the first-order aberration. Following our previous publication on the principle of non-imaging focusing heliostat, this paper further explores higher order residual aberration that limits the size of the focusing spot. The residual aberration can be partially corrected by offsetting the pivot point of mirrors and pre-setting the tilting angles of mirrors.

  19. FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis.

    Directory of Open Access Journals (Sweden)

    Alex D Herbert

    Full Text Available Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ.

  20. Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: processing at transcription sites or accumulation in SC35 foci.

    Science.gov (United States)

    Pawlicki, Jan M; Steitz, Joan A

    2009-02-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate expression of their target messenger RNAs. We recently demonstrated that primary miRNA transcripts (pri-miRNAs) retained at transcription sites are processed with enhanced efficiency, suggesting that pri-miRNA processing is coupled to transcription in mammalian cells. We also observed that transiently expressed pri-miRNAs accumulate in nuclear foci with splicing factor SC35 and Microprocessor components, Drosha and DGCR8. Here, we show that pri-miRNAs containing a self-cleaving hepatitis delta ribozyme accumulate in the nucleoplasm after release from their transcription sites, but are not efficiently processed. Pri-miRNAs with ribozyme-generated 3' ends do not localize to SC35-containing foci, whereas cleaved and polyadenylated pri-miRNA transcripts with or without the pre-miRNA hairpin do. Pri-miRNA/SC35 foci contain a number of proteins normally associated with SC35 domains, including ASF/SF2, PABII, and the prolyl isomerase, Pin1. In contrast, RNA polymerase II and PM/Scl-100 do not strongly colocalize with pri-miRNAs in SC35-containing foci. These data argue that pri-miRNA/SC35-containing foci are not major sites of pri-miRNA processing and that pri-miRNA processing is coupled to transcription. We discuss the implications of our findings relative to recent insights into miRNA biogenesis, mRNA metabolism, and the nuclear organization of gene expression.

  1. Intracellular Ca(2+) and Zn(2+) signals during monochloramine-induced oxidative stress in isolated rat colon crypts.

    Science.gov (United States)

    Cima, Robert R; Dubach, J Matthew; Wieland, Aaron M; Walsh, Breda M; Soybel, David I

    2006-02-01

    During acute exacerbations of inflammatory bowel diseases, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the colon mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH(2)Cl), to serve as agonists of Ca(2+) and Zn(2+) accumulation within the colonocyte. Individual colon crypts prepared from Sprague-Dawley rats were mounted in perfusion chambers after loading with fluorescent reporters fura 2-AM and fluozin 3-AM. These reporters were characterized, in situ, for responsiveness to Ca(2+) and Zn(2+) in the cytoplasm. Responses to different concentrations of NH(2)Cl (50, 100, and 200 microM) were monitored. Subsequent studies were designed to identify the sources and mechanisms of NH(2)Cl-induced increases in Ca(2+) and Zn(2+) in the cytoplasm. Exposure to NH(2)Cl led to dose-dependent increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) in the range of 200-400 nM above baseline levels. Further studies indicated that NH(2)Cl-induced accumulation of Ca(2+) in the cytoplasm is the result of release from intracellular stores and basolateral entry of extracellular Ca(2+) through store-operated channels. In addition, exposure to NH(2)Cl resulted in dose-dependent and sustained increases in intracellular Zn(2+) concentration ([Zn(2+)](i)) in the nanomolar range. These alterations were neutralized by dithiothreitol, which shields intracellular thiol groups from oxidation. We conclude that Ca(2+)- and Zn(2+)-handling proteins are susceptible to oxidation by chloramines, leading to sustained, but not necessarily toxic, increases in [Ca(2+)](i) and [Zn(2+)](i). Under certain conditions, NH(2)Cl may act not as a toxin but as an agent that activates intracellular signaling pathways.

  2. The cAMP-regulated and 293B-inhibited K+ conductance of rat colonic crypt base cells.

    Science.gov (United States)

    Warth, R; Riedemann, N; Bleich, M; Van Driessche, W; Busch, A E; Greger, R

    1996-05-01

    We have shown previously that secretagogues acting via the second messenger adenosine 3',5'-cyclic monophosphate (cAMP) activate, besides their marked effect on the luminal Cl- conductance, a K+ conductance in the basolateral membrane of colonic crypt cells. This conductance is blocked by the chromanol 293B. This K+ conductance is examined here in more detail in cell-attached (c.a.) and cell-excised (c.e.) patch- clamp studies. Addition of forskolin (5 micromol/l) to the bath led to the activation of very small-conductance (probably Hz (n = 30). The current/voltage curves of this noise indicated that the underlying ion channels were K+ selective. 293B reduced the power density of the noise (So) to 46 +/- 8.7% of its control value and shifted fc from 291 +/- 26 to 468 +/- 54 Hz (n = 8). In c.e. patches from cells previously stimulated by forskolin, the same type of current persisted in 3 out of 18 experiments when the bath solution was a cytosolic-type solution without adenosine 5'-triphosphate (ATP) (CYT). In 15 experiments the addition of ATP (1 mmol/l) to CYT solution was necessary to induce or augment channel activity. In six experiments excision was performed into CYT + ATP solution and channel activity persisted. 293B exerted a reversible inhibitory effect. The channel activity was reduced by 5 mmol/l Ba2+ and was completely absent when K+ in the bath was replaced by Na+. These data suggest that forskolin activates a K+ channel of very small conductance which can be inhibited directly and reversibly by 293B.

  3. High order aberration and straylight evaluation after cataract surgery with implantation of an aspheric,aberration correcting monofocal intraocular lens

    Institute of Scientific and Technical Information of China (English)

    Florian; T; A; Kretz; Tamer; Tandogan; Ramin; Khoramnia; Gerd; U; Auffarth

    2015-01-01

    ·AIM: To evaluate the quality of vision in respect to high order aberrations and straylight perception after implantation of an aspheric, aberration correcting,monofocal intraocular lens(IOL).·METHODS: Twenty-one patients(34 eyes) aged 50 to83 y underwent cataract surgery with implantation of an aspheric, aberration correcting IOL(Tecnis ZCB00,Abbott Medical Optics). Three months after surgery they were examined for uncorrected(UDVA) and corrected distance visual acuity(CDVA), contrast sensitivity(CS)under photopic and mesopic conditions with and without glare source, ocular high order aberrations(HOA, Zywave II) and retinal straylight(C-Quant).· RESULTS: Postoperatively, patients achieved a postoperative CDVA of 0.0 log MAR or better in 97.1% of eyes. Mean values of high order abberations were +0.02±0.27(primary coma components) and-0.04 ±0.16(spherical aberration term). Straylight values of the C-Quant were 1.35±0.44 log which is within normal range of age matched phakic patients. The CS measurements under mesopic and photopic conditions in combination with and without glare did not show any statistical significance in the patient group observed(P ≥0.28).· CONCLUSION: The implantation of an aspherical aberration correcting monofocal IOL after cataractsurgery resulted in very low residual higher order aberration(HOA) and normal straylight.

  4. 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.

  5. 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

  6. Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that ...

    African Journals Online (AJOL)

    Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that should be ... of the retroesophageal space during esophagectomy, may prevent any injury to the .... Source of Support: Nil, Conflict of Interest: None declared. [Downloaded free ...

  7. 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.

  8. Automated computational aberration correction method for broadband interferometric imaging techniques.

    Science.gov (United States)

    Pande, Paritosh; Liu, Yuan-Zhi; South, Fredrick A; Boppart, Stephen A

    2016-07-15

    Numerical correction of optical aberrations provides an inexpensive and simpler alternative to the traditionally used hardware-based adaptive optics techniques. In this Letter, we present an automated computational aberration correction method for broadband interferometric imaging techniques. In the proposed method, the process of aberration correction is modeled as a filtering operation on the aberrant image using a phase filter in the Fourier domain. The phase filter is expressed as a linear combination of Zernike polynomials with unknown coefficients, which are estimated through an iterative optimization scheme based on maximizing an image sharpness metric. The method is validated on both simulated data and experimental data obtained from a tissue phantom, an ex vivo tissue sample, and an in vivo photoreceptor layer of the human retina.

  9. Anisoplanatism in adaptive optics systems due to pupil aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Bauman, B

    2005-08-01

    Adaptive optics systems typically include an optical relay that simultaneously images the science field to be corrected and also a set of pupil planes conjugate to the deformable mirror of the system. Often, in the optical spaces where DM's are placed, the pupils are aberrated, leading to a displacement and/or distortion of the pupil that varies according to field position--producing a type of anisoplanatism, i.e., a degradation of the AO correction with field angle. The pupil aberration phenomenon is described and expressed in terms of Seidel aberrations. An expression for anisoplanatism as a function of pupil distortion is derived, an example of an off-axis parabola is given, and a convenient method for controlling pupil-aberration-generated anisoplanatism is proposed.

  10. Automated spherical aberration correction in scanning confocal microscopy

    NARCIS (Netherlands)

    Yoo, H.W.; Royen, M.E.; van Cappellen, W.A.; Houtsmuller, A.B.; Verhaegen, M.H.G.; Schitter, G.

    2014-01-01

    Mismatch between the refractive indexes of immersion media and glass coverslips introduces spherical aberrations in microscopes especially for high numerical aperture objectives. This contribution demonstrates an automated adjustment of the coverslip correction collar in scanning confocal microscopy

  11. 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...... effciency, the optimum truncation of the transmit beam and the spatial sensitivity of a CW coherent lidar system. Under strong degree of aberration, the spatial confinement is significantly degraded. However for SA, the degradation of the spatial confinement can be reduced by tuning the truncation...

  12. Intrinsic Third Order Aberrations in Electrostatic and Magnetic Quadrupoles

    CERN Document Server

    Baartman, R

    2015-01-01

    Intrinsic aberrations are those which occur due to the finite length of the desired field configuration. They are often loosely ascribed to the fringing field. This is misleading as it implies that the effects can be minimized by shaping the fields. In fact, there is an irreducible component related to the broken symmetry. It is present even in the hard-edge limit, and moreover, the other (soft-edge) effects can be simply ascribed to the intrinsic aberration spread over a finite length. We rederive the aberration formulas for quadrupoles using a Hamiltonian formalism. This allows for an easy comparison of electrostatic and magnetic quadrupoles. For different combinations of large and small emittances in the two transverse planes, it is found that in some situations electrostatic quadrupoles have lower aberrations, while in others, magnetic quadrupoles are better. As well, we discuss the ways in which existing transport codes handle quadrupole fringe fields. Pitfalls are pointed out and improvements proposed.

  13. 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.

  14. CYTOGENETIC STUDY OF CHROMOSOMAL ABERRATIONS ASSOCIATED WITH CHRONIC LEUKEMIA

    National Research Council Canada - National Science Library

    Dharma Niranjan Mishra; Sitansu Kumar Panda; Saurjya Ranjan Das; Jami Sagar Prusti; Santosh Sahu; Priyambada Panda; Chinmayi Mohapatra

    2016-01-01

    ... in the Hematology section of Pathology Department from the coastal District of Orissa. The chromosomal aberrations were taken into account in this present study and arranged in tables, Bar charts and Pie charts for comparison...

  15. Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning

    Science.gov (United States)

    Wolf, Benita; Diop, Fodé; Ferraris, Pauline; Wichit, Sineewanlaya; Busso, Coralie; Missé, Dorothée

    2017-01-01

    Zika virus (ZIKV) causes congenital microcephaly. Although ZIKV can impair cell cycle progression and provoke apoptosis, which probably contributes to disease aetiology through depletion of neural progenitor cells, additional cellular mechanisms may be important. Here, we investigated whether ZIKV infection alters centrosome number and spindle positioning, because such defects are thought to be at the root of inherited primary autosomal recessive microcephaly (MCPH). In addition to HeLa cells, in which centrosome number and spindle positioning can be well monitored, we analysed retinal epithelial cells (RPE-1), as well as brain-derived microglial (CHME-5) and neural progenitor (ReN) cells, using immunofluorescence. We established that ZIKV infection leads to supernumerary foci containing centriolar proteins that in some cases drive multipolar spindle assembly, as well as spindle positioning defects in HeLa, RPE-1 and CHME-5 cells, but not in ReN cells. We uncovered similar phenotypes in HeLa cells upon infection with dengue virus (DENV-2), another flavivirus that does not target brain cells and does not cause microcephaly. We conclude that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika. PMID:28100662

  16. Contrasting sylvatic foci of Venezuelan equine encephalitis virus in northern South America.

    Science.gov (United States)

    Barrera, Roberto; Ferro, Cristina; Navarro, Juan-Carlos; Freier, Jerome; Liria, Jonathan; Salas, Rosalba; Ahumada, Marta; Vasquez, Clovis; Gonzalez, Marta; Kang, Wenli; Boshell, Jorge; Weaver, Scott C

    2002-09-01

    The ecology of Venezuelan equine encephalitis (VEE) virus transmission was compared at three enzootic foci: two forest sites in the Catatumbo region of western Venezuela that have yielded small numbers of virus isolates since the 1970s, and another focus in the middle Magdalena Valley of Colombia that has consistently yielded many VEE virus isolates. Our results demonstrated dramatic differences in VEE virus isolation rates from sentinel hamsters, as well as differences in mosquito species composition and captured mammals with antibodies to VEE virus, between the Colombian and Venezuelan study sites. The higher isolation rate of enzootic VEE virus in the Colombian site was associated with a more abundant fauna of spiny rats (Proechimys spp.), known reservoir hosts of enzootic VEE virus. Mosquito collections demonstrated that the Colombian forest had a higher mosquito diversity and species evenness than either of the Venezuelan forests. The Colombian focus was especially richer in its Culex (Melanoconion) spp. fauna, a subgenus that includes all proven enzootic vectors for VEE virus. Our results suggest that the greater abundance, diversity, and stability of enzootic vector populations, combined with the greater density of rodent reservoir hosts, explains the higher levels of VEE virus circulation in the Colombian focus compared with the Venezuelan forests.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. In-vehicle extremity injuries from improvised explosive devices: current and future foci.

    Science.gov (United States)

    Ramasamy, Arul; Masouros, Spyros D; Newell, Nicolas; Hill, Adam M; Proud, William G; Brown, Katherine A; Bull, Anthony M J; Clasper, Jon C

    2011-01-27

    The conflicts in Iraq and Afghanistan have been epitomized by the insurgents' use of the improvised explosive device against vehicle-borne security forces. These weapons, capable of causing multiple severely injured casualties in a single incident, pose the most prevalent single threat to Coalition troops operating in the region. Improvements in personal protection and medical care have resulted in increasing numbers of casualties surviving with complex lower limb injuries, often leading to long-term disability. Thus, there exists an urgent requirement to investigate and mitigate against the mechanism of extremity injury caused by these devices. This will necessitate an ontological approach, linking molecular, cellular and tissue interaction to physiological dysfunction. This can only be achieved via a collaborative approach between clinicians, natural scientists and engineers, combining physical and numerical modelling tools with clinical data from the battlefield. In this article, we compile existing knowledge on the effects of explosions on skeletal injury, review and critique relevant experimental and computational research related to lower limb injury and damage and propose research foci required to drive the development of future mitigation technologies.

  2. Pattern of Chromosomal Aberrations in Patients from North East Iran

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey

    2013-01-01

    Full Text Available Objective: Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques.Materials and Methods: In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities.Results: The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS was the most prevalent autosomal aberration in the patients (77.1%. Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA. Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner’s syndrome and 33.5% had Klinefelter’s syndrome.Conclusion: According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  3. Aberrant cervical thymus mimicking thyroid on ultrasonography: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Sub; Park, Ju Hyun; Kim, Bong Soo; Park, Ji Kang; Choi, Jae Hyuck [Jeju National Univ. Hospital/Jeju National Univ. School of Medicine, Jeju (Korea, Republic of)

    2012-10-15

    Aberrant cervical thymus is rarely reported in adults. We report a case of solid aberrant cervical thymus in a 27 year old female, which was found incidentally on ultrasonography for the evaluation of the thyroid cancer. On ultrasonography, the lesion was found between the left thyroid and common carotid artery without any remarkable interface echo, and had similar echogenicity to the thyroid. The lesion extended to the upper pole of the left thyroid.

  4. Wide-angle chromatic aberration corrector for the human eye.

    Science.gov (United States)

    Benny, Yael; Manzanera, Silvestre; Prieto, Pedro M; Ribak, Erez N; Artal, Pablo

    2007-06-01

    The human eye is affected by large chromatic aberration. This may limit vision and makes it difficult to see fine retinal details in ophthalmoscopy. We designed and built a two-triplet system for correcting the average longitudinal chromatic aberration of the eye while keeping a reasonably wide field of view. Measurements in real eyes were conducted to examine the level and optical quality of the correction. We also performed some tests to evaluate the effect of the corrector on visual performance.

  5. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

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

    2015-01-01

    aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded...... poorly to in vivo chemotherapy treatment as compared with t(9;11) AML originating from HPCs....

  6. Study of the wavefront aberrations in children with amblyopia

    Institute of Scientific and Technical Information of China (English)

    ZHAO Peng-fei; ZHOU Yue-hua; WANG Ning-li; ZHANG Jing

    2010-01-01

    Background Amblyopia is a common ophthalmological condition and the wavefront aberrometer is a relatively new diagnostic tool used globally to measure optical characteristics of human eyes as well as to study refractive errors in amblyopic eyes. We studied the wavefront aberration of the amblyopic children's eyes and analyzed the mechanism of the wavefront aberration in the formation of the amblyopia, try to investigate the new evidence of the treatment of the amblyopia, especially in the refractory amblyopia.Methods The WaveScan Wavefront System (VISX, USA) aberrometer was used to investigate four groups of children under dark accommodation and cilliary muscle paralysis. There were 45 cases in the metropic group, 87 in the amblyopic group, 92 in the corrected-amblyopic group and 38 in the refractory amblyopic group. One-way analysis of variance (ANOVA), t-test and multivariate linear regression were used to analyze all the data.Results Third order to 6th order aberrations showed a decreasing trend whereas in the higher order aberrations the main ones were 3rd order coma (Z3-1-Z31), trefoil (Z3-3-Z33) and 4th order aberration (Z40); and 3rd order coma represented the highest percentage of all three main aberrations. Within 3rd order coma, vertical coma (Z3-1) accounted for a greater percentage than horizontal coma (Z31). Significant differences of vertical coma were found among all clinical groups of children: vertical coma in the amblyopic group (0.17±0.15) was significantly higher than in the metropic group (0.11±0.13, P0.05).Conclusions Although lower order aberrations such as defocus (myopia and hyperopia) and astigmatism are major factors determining the quality of the retinal image, higher order aberrations also need to be considered in amblyopic eyes as their effects are significant.

  7. Multiplexed aberration measurement for deep tissue imaging in vivo

    OpenAIRE

    Wang, Chen; Liu, Rui; Milkie, Daniel E; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

    2014-01-01

    We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large...

  8. Multiplexed aberration measurement for deep tissue imaging in vivo

    Science.gov (United States)

    Wang, Chen; Liu, Rui; Milkie, Daniel E.; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

    2014-01-01

    We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large imaging volume. PMID:25128976

  9. Longitudinal Trajectories of Aberrant Behavior in Fragile X Syndrome

    OpenAIRE

    Hustyi, Kristin M; Hall, Scott S.; Jo, Booil; Lightbody, Amy A; Reiss, Allan L.

    2014-01-01

    The Aberrant Behavior Checklist—Community (ABC-C; Aman, Burrow, & Wolford, 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 ...

  10. Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia.

    Science.gov (United States)

    Pal, Arnab; Srivastava, Tapasya; Sharma, Manish K; Mehndiratta, Mohit; Das, Prerna; Sinha, Subrata; Chattopadhyay, Parthaprasad

    2010-11-01

    Hypoxia is an integral part of tumorigenesis and contributes extensively to the neoplastic phenotype including drug resistance and genomic instability. It has also been reported that hypoxia results in global demethylation. Because a majority of the cytosine-phosphate-guanine (CpG) islands are found within the repeat elements of DNA, and are usually methylated under normoxic conditions, we suggested that retrotransposable Alu or short interspersed nuclear elements (SINEs) which show altered methylation and associated changes of gene expression during hypoxia, could be associated with genomic instability. U87MG glioblastoma cells were cultured in 0.1% O₂ for 6 weeks and compared with cells cultured in 21% O₂ for the same duration. Real-time PCR analysis showed a significant increase in SINE and reverse transcriptase coding long interspersed nuclear element (LINE) transcripts during hypoxia. Sequencing of bisulphite treated DNA as well as the Combined Bisulfite Restriction Analysis (COBRA) assay showed that the SINE loci studied underwent significant hypomethylation though there was patchy hypermethylation at a few sites. The inter-alu PCR profile of DNA from cells cultured under 6-week hypoxia, its 4-week revert back to normoxia and 6-week normoxia showed several changes in the band pattern indicating increased alu mediated genomic alteration. Our results show that aberrant methylation leading to increased transcription of SINE and reverse transcriptase associated LINE elements could lead to increased genomic instability in hypoxia. This might be a cause of genetic heterogeneity in tumours especially in variegated hypoxic environment and lead to a development of foci of more aggressive tumour cells.

  11. Aberrant Glycosylation as Biomarker for Cancer: Focus on CD43

    Directory of Open Access Journals (Sweden)

    Franca Maria Tuccillo

    2014-01-01

    Full Text Available Glycosylation is a posttranslational modification of proteins playing a major role in cell signalling, immune recognition, and cell-cell interaction because of their glycan branches conferring structure variability and binding specificity to lectin ligands. Aberrant expression of glycan structures as well as occurrence of truncated structures, precursors, or novel structures of glycan may affect ligand-receptor interactions and thus interfere with regulation of cell adhesion, migration, and proliferation. Indeed, aberrant glycosylation represents a hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis pathways such as the altered expression of glycosyltransferases and glycosidases. Most studies have been carried out to identify changes in serum glycan structures. In most cancers, fucosylation and sialylation are significantly modified. Thus, aberrations in glycan structures can be used as targets to improve existing serum cancer biomarkers. The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. In this review, we discuss the aberrant protein glycosylation associated with human cancer and the identification of protein glycoforms as cancer biomarkers. In particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker and the potential to exploit the UN1 monoclonal antibody (UN1 mAb to identify aberrant CD43 glycoforms.

  12. Dimensions of driving anger and their relationships with aberrant driving.

    Science.gov (United States)

    Zhang, Tingru; Chan, Alan H S; Zhang, Wei

    2015-08-01

    The purpose of this study was to investigate the relationship between driving anger and aberrant driving behaviours. An internet-based questionnaire survey was administered to a sample of Chinese drivers, with driving anger measured by a 14-item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory Factor Analysis demonstrated that the three-factor model (hostile gesture, arrival-blocking and safety-blocking) of the DAS fitted the driving anger data well. The Exploratory Factor Analysis on DBQ data differentiated four types of aberrant driving, viz. emotional violation, error, deliberate violation and maintaining progress violation. For the anger-aberration relation, it was found that only "arrival-blocking" anger was a significant positive predictor for all four types of aberrant driving behaviours. The "safety-blocking" anger revealed a negative impact on deliberate violations, a finding different from previously established positive anger-aberration relation. These results suggest that drivers with different patterns of driving anger would show different behavioural tendencies and as a result intervention strategies may be differentially effective for drivers of different profiles.

  13. The Sommersdorf mummies-An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany.

    Science.gov (United States)

    Alterauge, Amelie; 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.

  14. CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice.

    Science.gov (United States)

    Riehl, Terrence E; Santhanam, Srikanth; Foster, Lynne; Ciorba, Matthew; Stenson, William F

    2015-12-01

    Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3-8 wk of age to wild-type, CD44(-/-), and TLR4(-/-) mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5(+) stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5(+) reporter mice from postnatal day 7 to day 14 decreased Lgr5(+) cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5(+) stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4.

  15. Description of a new species of Euderus Haliday from the southeastern United States (Hymenoptera, Chalcidoidea, Eulophidae): the crypt-keeper wasp

    Science.gov (United States)

    Egan, Scott P.; Weinersmith, Kelly L.; Liu, Sean; Ridenbaugh, Ryan D.; Zhang, Y. Miles; Forbes, Andrew A.

    2017-01-01

    Abstract A new species of the genus Euderus Haliday, Euderus set sp. n., is described and illustrated from the southeastern United States, where it parasitizes the crypt gall wasp, Bassettia pallida Ashmead, 1896, on live oaks in the genus Quercus (subsection Virentes). This is the 1st species of the genus reported from the southeastern United States to parasitize cynipid gall wasps and the 3rd species of the genus reported to attack cynipids in North America. Modified sections of the identification keys to subgenera and species of Euderus (Yoshimoto, 1971) are included to integrate the new species. PMID:28228666

  16. Optical aberrations of intraocular lenses measured in vivo and in vitro

    Science.gov (United States)

    Barbero, Sergio; Marcos, Susana; Jiménez-Alfaro, Ignacio

    2003-10-01

    Corneal and ocular aberrations were measured in a group of eyes before and after cataract surgery with spherical intraocular lens (IOL) implantation by use of well-tested techniques developed in our laboratory. By subtraction of corneal from total aberration maps, we also estimated the optical quality of the intraocular lens in vivo. We found that aberrations in pseudophakic eyes are not significantly different from aberrations in eyes before cataract surgery or from previously reported aberrations in healthy eyes of the same age. However, aberrations in pseudophakic eyes are significantly higher than in young eyes. We found a slight increase of corneal aberrations after surgery. The aberrations of the IOL and the lack of balance of the corneal spherical aberrations by the spherical aberrations of the intraocular lens also degraded the optical quality in pseudophakic eyes. We also measured the aberrations of the IOL in vitro, using an eye cell model, and simulated the aberrations of the IOL on the basis of the IOL's physical parameters. We found a good agreement among in vivo, in vitro, and simulated measures of spherical aberration: Unlike the spherical aberration of the young crystalline lens, which tends to be negative, the spherical aberration of the IOL is positive and increases with lens power. Computer simulations and in vitro measurements show that tilts and decentrations might be contributors to the increased third-order aberrations in vivo in comparison with in vitro measurements.

  17. Persistence of Early Emerging Aberrant Behavior in Children with Developmental Disabilities

    Science.gov (United States)

    Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff

    2005-01-01

    This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant Behavior…

  18. [A study on the taxonomy of soil amoebas from Caspian plague foci based on an analysis of ribosomal operon sequences].

    Science.gov (United States)

    Koshel', E I; Anisimova, L V; Novichkova, L A; Vidiaeva, N A; Guseva, N P; Eroshenko, G A; Kutyrev, V V

    2015-01-01

    The results of a study on the taxonomy and quantitative abundance of free-living amoebas in soil samples from the Russian plague foci of the northwestern Caspian steppe, the Caspian sand, and the Volga-Ural steppe are presented. Amoebas of the Willaertia and Hartmanella genera, as well as representatives of myxomycetes, were isolated from samples. From these, amoebas of the Acanthamoeba genus predominated and could be as abundantas 300000 cells per 1 g of soil. Sequencing of the 18S rRNA gene region showed that Acanthamoeba from the Volga-Ural steppe focus belonged to the A. castellanii species. Phylogenetic analysis confirmed that amoebas from two other Caspian foci belonged to the species of Acanthamoeba spp.

  19. PROBLEMS OF GEOLOGICAL INTERPRETATION OF SEISMIC-FOCI SYSTEMS OF THE EARTH’S CRUST (GEOMECHANICS AND TECTONOPHYSICAL ANALYSIS

    Directory of Open Access Journals (Sweden)

    Boris M. Chikov

    2015-09-01

    Full Text Available In our study, an earthquake focus is viewed as a 3D zone of the Earth’s crust, wherein the discharge of mechanical loading is accompanied by recordable destruction and qualitative transformation of the geological medium. The purpose of the present publication is to make an attempt to reveal a direct relationship between seismicity and deformation-metamorphic processes which took place in the Earth’s crust. Traditional and alternative interpretations of geomechanics of seismic-foci situations are discussed. The problems of geodynamics and geostatics of the seismic-foci systems and their concentrations, as well as anthropogenic models and mechanisms of focus medium structuring are reviewed. The relationship between seismicity and mechanisms of «regional shearing» or formation of crustal deformation-metamorphic structures of lineament type is outlined in the example of the Chuya seismic system of earthquakes which occurred in 2003 and afterwards in the Altai region.

  20. 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.

  1. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

    Science.gov (United States)

    Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

    2015-09-29

    Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

  2. 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

    2016-01-01

    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. PMID:27445126

  3. 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.

  4. RNA/MBNL1-containing foci in myoblast nuclei from patients affected by myotonic dystrophy type 2: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    F. Perdoni

    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.

  5. 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

  6. Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)

    2011-09-15

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using {gamma}-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  7. Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors

    OpenAIRE

    Urani, Chiara; Corvi, Raffaella; CALLEGARO G.; Stefanini, Federico Mattia

    2013-01-01

    In vitro cell transformation assays (CTAs) have been shown to model important stages of in vivo carcinogenesis and have the potential to predict carcinogenicity in humans. Advantages of CTAs are their ability of revealing both genotoxic and non-genotoxic carcinogens while reducing both experimental costs and the number of animals used. The endpoint of the CTA is foci formation, and requires classification under light microscopy based on morphology. Thus current limitations for the wide ado...

  8. 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.

  9. Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy.

    Science.gov (United States)

    Kondo, Natsuko; Michiue, Hiroyuki; Sakurai, Yoshinori; Tanaka, Hiroki; Nakagawa, Yosuke; Watanabe, Tsubasa; Narabayashi, Masaru; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji

    2016-01-01

    In this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT. Boron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. (10)B captures neutrons and produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation. We analyzed the number of γH2AX foci by immunohistochemistry 30 min or 24 h after neutron irradiation. In both normal brain and brain tumor, γH2AX foci induced by (10)B(n,α)(7)Li reaction remained 24 h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24 h after irradiation in these tissues. DSBs produced by (10)B(n,α)(7)Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24 h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by (10)B(n,α)(7)Li reaction.

  10. 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.

  11. Induction of chromosomal aberrations in human lymphocytes by fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da; Coelho, Paulo Rogerio Pinto; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br

    2009-07-01

    Chromosome aberrations induced by sparsely ionizing radiation (low-LET) are well known and cytogenetic analyses of irradiated human lymphocytes have been widely applied to biological dosimetry. However, much less is known about chromosome aberrations induced by densely ionizing radiation (high LET), such as that of alpha particles or neutrons. Such particles induce DNA strand breaks, as well as chromosome breakage and rearrangements of high complexity. This damage is more localized and less efficiently repaired than after X- or {gamma}-ray irradiation. This preferential production of complex aberrations by densely ionizing radiation is related to the unique energy deposition patterns, which produces highly localized multiple DNA damage at the chromosomal level. A better knowledge of the interactions between different types of radiation and cellular DNA is of importance, not only from the radiobiological viewpoint but also for dosimetric and therapeutic purposes. The objective of the present study was to analyse the cytogenetic effects of fission neutrons on peripheral blood lymphocytes in order to evaluate structural and numerical aberrations and number of cells in the different mitotic cycles. So, blood samples from five healthy donors, 22-25 years old, of both sexes, were irradiated in the Research Reactor IEA-R1 of our Institute (IPEN/CNEN-SP) with thermal and fast neutrons at doses of 0.2; 0.3; 0.5 and 1.0 Gy. The {gamma} contribution to the total absorbed dose was about 30%. These doses were monitored by thermoluminescent dosemeters: LiF-600 (for neutrons) and LiF-700 (for {gamma}-rays). The data concerning structural aberrations were evaluated with regard to three parameters: percentage of cells with aberrations, number of aberrations/cell and number of dicentric/cell. The cytogenetic results showed an increase in the three parameters after irradiation with neutrons, as a function of radiation dose. Apparently, there was no influence of neutrons on the

  12. 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.

  13. The historical distribution of main malaria foci in Spain as related to water bodies.

    Science.gov (United States)

    Sousa, Arturo; García-Barrón, Leoncio; Vetter, Mark; Morales, Julia

    2014-08-06

    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.

  14. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells.

    Science.gov (United States)

    Vaurijoux, Aurelie; Voisin, Pascale; Freneau, Amelie; Barquinero, Joan Francesc; Gruel, Gaetan

    2017-03-01

    Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5Gy had at least one of these persistent IRIF 24h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci

    Directory of Open Access Journals (Sweden)

    Wu Yih-Ru

    2009-02-01

    Full Text Available Abstract Background Spinocerebellar ataxia type 8 (SCA8 involves the expression of an expanded CTG/CAG combined repeats (CR from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS and a polyglutamine expansion protein (ataxin 8, ATXN8. The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad. Results Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR. Conclusion The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.

  16. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  17. Helicobacter hepaticus infection promotes hepatitis and preneoplastic foci in farnesoid X receptor (FXR deficient mice.

    Directory of Open Access Journals (Sweden)

    Alton G Swennes

    Full Text Available Farnesoid X receptor (FXR is a nuclear receptor that regulates bile acid metabolism and transport. Mice lacking expression of FXR (FXR KO have a high incidence of foci of cellular alterations (FCA and liver tumors. Here, we report that Helicobacter hepaticus infection is necessary for the development of increased hepatitis scores and FCA in previously Helicobacter-free FXR KO mice. FXR KO and wild-type (WT mice were sham-treated or orally inoculated with H. hepaticus. At 12 months post-infection, mice were euthanized and liver pathology, gene expression, and the cecal microbiome were analyzed. H. hepaticus induced significant increases hepatitis scores and FCA numbers in FXR KO mice (P<0.01 and P<0.05, respectively. H. hepaticus altered the beta diversity of cecal microbiome in both WT and FXR KO mice compared to uninfected mice (P<0.05. Significant upregulation of β-catenin, Rela, Slc10a1, Tlr2, Nos2, Vdr, and Cyp3a11 was observed in all FXR KO mice compared to controls (P<0.05. Importantly, H. hepaticus and FXR deficiency were necessary to significantly upregulate Cyp2b10 (P<0.01. FXR deficiency was also a potent modulator of the cecal microbiota, as observed by a strong decrease in alpha diversity. A significant decrease in Firmicutes, particularly members of the order Clostridiales, was observed in FXR KO mice (P<0.05 and FDR<5%, ANOVA. While FXR deficiency strongly affects expression of genes related to immunity and bile acid metabolism, as well as the composition of the microbiome; however, its deficiency was not able to produce significant histopathological changes in the absence of H. hepaticus infection.

  18. Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

    Science.gov (United States)

    Simon, Stéphanie; Demeure, Christian; Lamourette, Patricia; Filali, Sofia; Plaisance, Marc; Créminon, Christophe; Volland, Hervé; Carniel, Elisabeth

    2013-01-01

    Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick) for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA), a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs). PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA) and an immunostrip (PLA-dipstick), usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition). They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples. PMID:23383008

  19. 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.

  20. 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.

  1. Fast and simple detection of Yersinia pestis applicable to field investigation of plague foci.

    Directory of Open Access Journals (Sweden)

    Stéphanie Simon

    Full Text Available Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA, a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs. PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA and an immunostrip (PLA-dipstick, usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition. They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples.

  2. Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.

    Science.gov (United States)

    Zhai, Yi; Wang, Yan; Wang, Zhaoqi; Liu, Yongji; Zhang, Lin; He, Yuanqing; Chang, Shengjiang

    2014-01-01

    An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.

  3. Chromosome aberrations as biomarkers of radiation exposure: Modelling basic mechanisms

    Science.gov (United States)

    Ballarini, F.; Ottolenghi, A.

    The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

  4. Antimutagenic potential of curcumin on chromosomal aberrations in Allium cepa

    Institute of Scientific and Technical Information of China (English)

    RAGUNATHAN Irulappan; PANNEERSELVAM Natarajan

    2007-01-01

    Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 μg/ml for 3 h and curcumin was given at 5, 10 and 20 μg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 μg/ml in Allium cepa root meristem cells.

  5. Spherical aberration and other higher-order aberrations in the human eye : from summary wave-front analysis data to optical variables relevant to visual perception

    NARCIS (Netherlands)

    Jansonius, Nomdo M.

    2010-01-01

    Wave-front analysis data from the human eye are commonly presented using the aberration coefficient c(4)(0) (primary spherical aberration) together with an overall measure of all higher-order aberrations. If groups of subjects are compared, however, the relevance of an observed difference cannot eas

  6. Correction of low order aberrations using continuous deformable mirrors.

    Science.gov (United States)

    Vdovin, Gleb; Soloviev, Oleg; Samokhin, Alexander; Loktev, Mikhail

    2008-03-03

    By analyzing the Poisson equation describing the static behavior of membrane and bimorph deformable mirrors and biharmonic equation describing the continuous facesheet mirror with push-pull actuators, we found that to achieve a high quality correction of low-order aberrations these mirrors should have sufficient number of actuators positioned outside the correction aperture. In particular, any deformable mirror described by the Poisson equation requires at least two actuators to be placed outside the working aperture per period of the azimuthal aberration of the highest expected order. Any deformable mirror described by the biharmonic equation, such as a continuous facesheet mirror with push-pull actuators, requires at least four actuators to be placed outside the working aperture per period of the azimuthal aberration of the highest expected order, and these actuators should not be positioned on a single circle.

  7. Non-Gaussianity and CMB aberration and Doppler

    CERN Document Server

    Catena, Riccardo; Notari, Alessio; Renzi, Alessandro

    2013-01-01

    The peculiar motion of an observer with respect to the CMB rest frame induces a deflection in the arrival direction of the observed photons (also known as CMB aberration) and a Doppler shift in the measured photon frequencies. As a consequence, aberration and Doppler effects induce non trivial correlations between the harmonic coefficients of the observed CMB temperature maps. In this paper we investigate whether these correlations generate a bias on Non-Gaussianity estimators $f_{NL}$. We perform this analysis simulating a large number of temperature maps with Planck-like resolution (lmax $= 2000$) as different realizations of the same cosmological fiducial model (WMAP7yr). We then add to these maps aberration and Doppler effects employing a modified version of the HEALPix code. We finally evaluate a generalization of the Komatsu, Spergel and Wandelt Non-Gaussianity estimator for all the simulated maps, both when peculiar velocity effects have been considered and when these phenomena have been neglected. Usi...

  8. An approach to remove defocused aberration on array confocal microscope

    Science.gov (United States)

    Huang, Xiangdong; Zhou, Tong; Jia, Jingguo

    2013-01-01

    In order to obtain a high resolution image required for ultra-precision measurement of microstructural object, a new approach is proposed for 3D microstructures. It uses the modulation transfer function with defocus aberration based on the ambiguity function and stable phase principle to achieve an optical phase filter, and utilizes generalized a spheric phase optical element to encode defocus images, and uses deconvolution technology to recover the images. In comparison with conventional optical system, the phase filter used in the optical system can make focal spot smaller when measure object defocusing, eliminates the effect of the defocus aberration, and improves the defocused property. Numerical results indicate the designed phase filter can improve lateral resolution of optical system, and the axial resolution of the optical system is not affect by the filter and defocus aberration. For different defocus plate, the phase filter can make character of modulation transfer function of lateral direction uniform approximation.

  9. Dynamic compensation of chromatic aberration in a programmable diffractive lens.

    Science.gov (United States)

    Millán, María S; Otón, Joaquín; Pérez-Cabré, Elisabet

    2006-10-02

    A proposal to dynamically compensate chromatic aberration of a programmable phase Fresnel lens displayed on a liquid crystal device and working under broadband illumination is presented. It is based on time multiplexing a set of lenses, designed with a common focal length for different wavelengths, and a tunable spectral filter that makes each sublens work almost monochromatically. Both the tunable filter and the sublens displayed by the spatial light modulator are synchronized. The whole set of sublenses are displayed within the integration time of the sensor. As a result the central order focalization has a unique location at the focal plane and it is common for all selected wavelengths. Transversal chromatic aberration of the polychromatic point spread function is reduced by properly adjusting the pupil size of each sublens. Longitudinal chromatic aberration is compensated by making depth of focus curves coincident for the selected wavelengths. Experimental results are in very good agreement with theory.

  10. Measuring chromatic aberrations in imaging systems using plasmonic nanoparticles

    Science.gov (United States)

    Gennaro, Sylvain D.; Roschuk, Tyler R.; Maier, Stefan A.; Oulton, Rupert F.

    2016-04-01

    Chromatic aberration in optical systems arises from the wavelength dependence of a glass's refractive index. Polychromatic rays incident upon an optical surface are refracted at slightly different angles and in traversing an optical system follow distinct paths creating images displaced according to color. Although arising from dispersion, it manifests as a spatial distortion correctable only with compound lenses with multiple glasses and accumulates in complicated imaging systems. While chromatic aberration is measured with interferometry, simple methods are attractive for their ease of use and low cost. In this letter we retrieve the longitudinal chromatic focal shift of high numerical aperture (NA) microscope objectives from the extinction spectra of metallic nanoparticles within the focal plane. The method is accurate for high NA objectives with apochromatic correction, and enables rapid assessment of the chromatic aberration of any complete microscopy systems, since it is straightforward to implement

  11. Low chromatic aberration hexapole for molecular state selection

    Science.gov (United States)

    Ke, Yi; Deng, Xiao-Bing; Hu, Zhong-Kun

    2016-01-01

    In molecular beam state-selection experiments, the electrostatic hexapole acts as an optical lens, imaging molecules from the source to the focus. The molecular longitudinal velocity spread induces the phenomenon of chromatic aberration, which will reduce the state-selection purity. We propose a scheme which can effectively reduce the chromatic aberration by changing the hexapole voltage operating manner. The hexapole is already charged before molecules arrive at the entrance of the hexapole. When molecules are completely inside the hexapole, the voltage is switched off rapidly at an appropriate time. In this manner, faster molecules travel a longer hexapole focusing region than slower molecules. Therefore the focusing positions of molecules with different velocities become close. Numerical trajectory simulations of molecular state selection are carried out, and the results show that this low chromatic aberration hexapole can significantly improve the state purity from 46.2% to 87.0%.

  12. 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....

  13. 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.

  14. 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.

  15. 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....

  16. Differential aberration correction (DAC) microscopy: a new molecular ruler.

    Science.gov (United States)

    Vallotton, P

    2008-11-01

    Considerable efforts have been deployed towards measuring molecular range distances in fluorescence microscopy. In the 1-10 nm range, Förster energy transfer microscopy is difficult to beat. Above 300 nm, conventional diffraction limited microscopy is suitable. We introduce a simple experimental technique that allows bridging the gap between those two resolution scales in both 2D and 3D with a resolution of about 20 nm. The method relies on a computational approach to accurately correct optical aberrations over the whole field of view. The method is differential because the probes of interest are affected in exactly the same manner by aberrations as are the reference probes used to construct the aberration deformation field. We expect that this technique will have significant implications for investigating structural and functional questions in bio-molecular sciences.

  17. 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.

  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. Adaptive and aberrant reward prediction signals in the human brain

    Science.gov (United States)

    Roiser, Jonathan P.; Stephan, Klaas E.; den Ouden, Hanneke E.M.; Friston, Karl J.; Joyce, Eileen M.

    2010-01-01

    Theories of the positive symptoms of schizophrenia hypothesize a role for aberrant reinforcement signaling driven by dysregulated dopamine transmission. Recently, we provided evidence of aberrant reward learning in symptomatic, but not asymptomatic patients with schizophrenia, using a novel paradigm, the Salience Attribution Test (SAT). The SAT is a probabilistic reward learning game that employs cues that vary across task-relevant and task-irrelevant dimensions; it provides behavioral indices of adaptive and aberrant reward learning. As an initial step prior to future clinical studies, here we used functional magnetic resonance imaging to examine the neural basis of adaptive and aberrant reward learning during the SAT in healthy volunteers. As expected, cues associated with high relative to low reward probabilities elicited robust hemodynamic responses in a network of structures previously implicated in motivational salience; the midbrain, in the vicinity of the ventral tegmental area, and regions targeted by its dopaminergic projections, i.e. medial dorsal thalamus, ventral striatum and prefrontal cortex (PFC). Responses in the medial dorsal thalamus and polar PFC were strongly correlated with the degree of adaptive reward learning across participants. Finally, and most importantly, differential dorsolateral PFC and middle temporal gyrus (MTG) responses to cues with identical reward probabilities were very strongly correlated with the degree of aberrant reward learning. Participants who showed greater aberrant learning exhibited greater dorsolateral PFC responses, and reduced MTG responses, to cues erroneously inferred to be less strongly associated with reward. The results are discussed in terms of their implications for different theories of associative learning. PMID:19969090

  20. Characterization of enzootic foci of Venezuelan equine encephalitis virus in western Venezuela.

    Science.gov (United States)

    Barrera, R; Torres, N; Freier, J E; Navarro, J C; García, C Z; Salas, R; Vasquez, C; Weaver, S C

    2001-01-01

    The distribution of the sylvatic subtype ID Venezuelan equine encephalitis (VEE) viruses in the lowland tropical forests of western Venezuela was investigated using remote sensing and geographic information system technologies. Landsat 5 Thematic Mapper satellite imagery was used to study the reflectance patterns of VEE endemic foci and to identify other locations with similar reflectance patterns. Enzootic VEE virus variants isolated during this study are the closest genetic relatives of the epizootic viruses that emerged in western Venezuela during 1992-1993. VEE virus surveillance was conducted by exposing sentinel hamsters to mosquito bites and trapping wild vertebrates in seven forests identified and located by means of the satellite image. We isolated VEE viruses from 48 of a total of 1,363 sentinel hamsters in two of the forests on six occasions, in both dry and wet seasons. None of the 12 small vertebrates captured in 8,190 trap-nights showed signs of previous VEE virus infection. The satellite image was classified into 13 validated classes of land use/vegetation using unsupervised and supervised techniques. Data derived from the image consisted of the raw digital values of near- and mid-infrared bands 4, 5, and 7, derived Tasseled Cap indices of wetness, greenness, and brightness, and the Normalized Difference Vegetation Index. Digitized maps provided ancillary data of elevation and soil geomorphology. Image enhancement was applied using Principal Component Analysis. A digital layer of roads together with georeferenced images was used to locate the study sites. A cluster analysis using the above data revealed two main groups of dense forests separated by spectral properties, altitude, and soil geomorphology. Virus was isolated more frequently from the forest type identified on flat flood plains of main rivers rather than the forest type found on the rolling hills of the study area. The spatial analysis suggests that mosquitoes carrying the enzootic viruses

  1. Focus correction in an apodized system with spherical aberration.

    Science.gov (United States)

    Bernal-Molina, Paula; Castejón-Mochón, José Francisco; Bradley, Arthur; López-Gil, Norberto

    2015-08-01

    We performed a theoretical and computational analysis of the through-focus axial irradiance in a system with a Gaussian amplitude pupil function and fourth- and sixth-order spherical aberration (SA). Two cases are analyzed: low aberrated systems, and the human eye containing significant levels of SA and a natural apodization produced by the Stiles-Crawford effect. Results show that apodization only produces a refraction change of the plane that maximized the Strehl ratio for eyes containing significant levels of negative SA.

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

    CSIR Research Space (South Africa)

    Mafusire, C

    2011-07-01

    Full Text Available factor of aberrated truncated Gaussian laser beams Cosmas Mafusire1,2 and Andrew Forbes1,2,* 1Council for Scientific and Industrial Research National Laser Centre, P.O. Box 395, Pretoria, South Africa 2School of Physics, University of Kwa... is verified experimentally by implementing aberrations as digital holograms in the laboratory. ? 2011 Optical Society of America OCIS codes: 140.3295, 080.1005, 120.5050. 1. INTRODUCTION The laser beam quality factor (M2) is a useful parameter...

  3. [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

  4. Aberrations of the point spread function of a multimode fiber

    CERN Document Server

    Descloux, Adrien; Pinkse, Pepijn W H

    2016-01-01

    We investigate the point spread function of a multimode fiber. The distortion of the focal spot created on the fiber output facet is studied for a variety of the parameters. We develop a theoretical model of wavefront shaping through a multimode fiber and use it to confirm our experimental results and analyze the nature of the focal distortions. We show that aberration-free imaging with a large field of view can be achieved by using an appropriate number of segments on the spatial light modulator during the wavefront-shaping procedure. The results describe aberration limits for imaging with multimode fibers as in, e.g., microendoscopy.

  5. Chromosomal aberrations in plants under magnetic fluid influence

    Energy Technology Data Exchange (ETDEWEB)

    Pavel, Angela [University of Medicine and Pharmacy Gr.T. Popa, Fac. of Pharmacy, Iasi (Romania)]. E-mail: angelapavel04@yahoo.com; Creanga, Dorina-Emilia [Faculty of Physics, University of Al. I. Cuza, Bd. Copou 11A, Iasi (Romania)]. E-mail: dorinacreanga@yahoo.com

    2005-03-15

    The study was focussed on the influence of a petroleum magnetic fluid upon the cell proliferation in young plants of agricultural interest. Zea mays plants, in their early ontogenetic stages were treated with magnetic fluid in relatively low concentrations (up to 100{mu}l/l) and root meristem was investigated by cytogenetical methods. The cell proliferation rate was found significantly enhanced as well as the percentage of chromosomal aberrations. Micronuclei, bridges, chromosome fragments and three-polar anaphases were the main types of chromosomal aberrations.

  6. Double aberration correction in a low-energy electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Th., E-mail: schmidtt@fhi-berlin.mpg.de [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Marchetto, H.; Levesque, P.L. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Groh, U.; Maier, F. [Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Preikszas, D. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Carl Zeiss NTS GmbH, Carl-Zeiss-Strasse 56, D-73447 Oberkochen (Germany); Hartel, P.; Spehr, R. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Lilienkamp, G. [Technische Universitaet Clausthal, Physikalisches Institut, Leibnizstrasse 4, D-38678 (Germany); Engel, W. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Fink, R. [Universitaet Erlangen-Nuernberg, Physikalische Chemie II, Egerlandstrasse 3, D-91058 Erlangen (Germany); Bauer, E. [Technische Universitaet Clausthal, Physikalisches Institut, Leibnizstrasse 4, D-38678 (Germany); Arizona State University, Department of Physics, Tempe, AZ 85287 (United States); Rose, H. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Umbach, E. [Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Freund, H.-J. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany)

    2010-10-15

    The lateral resolution of a surface sensitive low-energy electron microscope (LEEM) has been improved below 4 nm for the first time. This breakthrough has only been possible by simultaneously correcting the unavoidable spherical and chromatic aberrations of the lens system. We present an experimental criterion to quantify the aberration correction and to optimize the electron optical system. The obtained lateral resolution of 2.6 nm in LEEM enables the first surface sensitive, electron microscopic observation of the herringbone reconstruction on the Au(1 1 1) surface.

  7. Pan-cancer analysis of ROS1 genomic aberrations

    OpenAIRE

    Wang, Yidan; 王奕丹

    2015-01-01

    The ROS proto-oncogene 1 (ROS1) encodes the ROS1 receptor kinase. ROS1 rearrangements are known to be oncogenic in glioblastoma, non–small-cell lung carcinoma (NSCLC) and cholangiocarcinoma. The clinical relevance of ROS1 genomic aberrations in other human cancers is largely unexamined. Here, we performed a pan-cancer analysis of ROS1 genomic aberrations across 20 cancer sites by interrogating the whole-exome sequencing data of the Cancer Genome Atlas (TCGA) via the cBioportal (www.cbioportal...

  8. 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.)

  9. 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...

  10. Effect of Coma Aberration on Orbital Angular Momentum Spectrum of Vortex Beams

    Institute of Scientific and Technical Information of China (English)

    CHEN Zi-Yang; PU Ji-Xiong

    2009-01-01

    Spiral spectra of vortex beams with coma aberration are studied.It is shown that the orbital angular momentum (OAM) states of vortex beams with coma aberration are different from those aberration-free vortex beams.Spiral spectra of beams with coma aberration are spreading.It is found that in the presence of coma aberration,the vortex beams contain not only the original OAM component but also other components.A larger coma aberration coefficient and/or a larger beam waist will lead to a wider spreading of the spiral spectrum. The results may have potential applications in information encoding and transmittance.

  11. Differential algebraic method for arbitrary order curvilinear-axis combined geometric-chromatic aberration analysis

    CERN Document Server

    Cheng Min; Lu Yi Long; Yao Zhen Hua

    2003-01-01

    The principle of differential algebra is applied to analyse and calculate arbitrary order curvilinear-axis combined geometric-chromatic aberrations of electron optical systems. Expressions of differential algebraic form of high order combined aberrations are obtained and arbitrary order combined aberrations can be calculated numerically. As an example, a typical wide electron beam focusing system with curved optical axes named magnetic immersion lens has been studied. All the second-order and third-order combined geometric-chromatic aberrations of the lens have been calculated, and the patterns of the corresponding geometric aberrations and combined aberrations have been given as well.

  12. 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.

  13. 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

  14. 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

  15. The Aberrant Salience Inventory: A New Measure of Psychosis Proneness

    Science.gov (United States)

    Cicero, David C.; Kerns, John G.; McCarthy, Denis M.

    2010-01-01

    Aberrant salience is the unusual or incorrect assignment of salience, significance, or importance to otherwise innocuous stimuli and has been hypothesized to be important for psychosis and psychotic disorders such as schizophrenia. Despite the importance of this concept in psychosis research, no questionnaire measures are available to assess…

  16. The pterygo-spinous muscle--an aberrant (atavic) remnant.

    Science.gov (United States)

    Nathan, H

    1989-01-01

    We report here on an aberrant pterygoid muscle found during a dissection of the infratemporal fossa. We have not noted such a muscle in hundreds of dissections in the area. A few anatomical texts (Piersol, 1911; Testut, Latarjet, 1931) have referred to its possible existence as the pterygo-spinous muscle.

  17. Polarization aberrations of radiation at the lens focus

    NARCIS (Netherlands)

    Sokolov, AL

    2005-01-01

    The polarization aberrations of radiation at the lens focus are calculated with allowance for diffraction effects. Calculations are performed using the representation of radiation as a coherent set of Hermite-Gauss modes with certain amplitudes, phases, and polarizations. An expression for the longi

  18. 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.

  19. Using Aberrant Behaviors as Reinforcers for Autistic Children.

    Science.gov (United States)

    Charlop, Marjorie H.; And Others

    1990-01-01

    Three experiments assessed the efficacy of various reinforcers to increase correct task responding in a total of 10 autistic children, aged 6-9. Of the reinforcers used (stereotypy, delayed echolalia, perseverative behavior, and food), task performance was highest with opportunities to engage in aberrant behaviors, and lowest with edible…

  20. 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...