Genetic and epigenetic mechanisms of tumor predisposition in hereditary non-polyposis colorectal carcinoma and sporadic cancers

Individuals with inherited deficiency in DNA mismatch repair(MMR) (Lynch syndrome) LS are predisposed to different cancers in a non-random fashion. Endometrial cancer (EC) is the most common extracolonic malignancy in LS. LS represents the best characterized form of hereditary nonpolyposis colorectal carcinoma (HNPCC). Other forms of familial non-polyposis colon cancer exist, including familial colorectal cancer type X (FCCX). This syndrome resembles LS, but MMR gene defects are excluded and the predisposition genes are unknown so far. To address why different organs are differently susceptible to cancer development, we examined molecular similarities and differences in selected cancers whose frequency varies in LS individuals. Tumors that are common (colorectal, endometrial, gastric) and less common (brain, urological) in LS were characterized for MMR protein expression, microsatellite instability (MSI), and by altered DNA methylation. We also studied samples of histologically normal endometrium, endometrial hyperplasia,and cancer for molecular alterations to identify potential markers that could predict malignant transformation in LS and sporadic cases. Our results suggest that brain and kidney tumors follow a different pathway for cancer development than the most common LS related cancers.Our results suggest also that MMR defects are detectable in endometrial tissues from a proportion of LS mutation carriers prior to endometrial cancer development. Traditionally (complex) atypical hyperplasia has been considered critical for progression to malignancy. Our results suggest that complex hyperplasia without atypia is equally important as a precursor lesion of malignancy. Tumor profiles from Egypt were compared with colorectal tumors from Finland to evaluate if there are differences specific to the ethnic origin (East vs.West). Results showed for the first time a distinct genetic and epigenetic signature in the Egyptian CRC marked by high methylation of microsatellite stable tumors associated with advanced stage, and low frequency of Wnt signaling activation, suggesting a novel pathway. DNA samples from FCCX families were studied with genome wide linkage analysis using microsatellite markers. Selected genes from the linked areas were tested for possible mutations that could explain predisposition to a large number of colon adenomas and carcinomas seen in these families. Based on the results from the linkage analysis, a number of areas with tentative linkage were identified in family 20. We narrowed down these areas by additional microsatellite markers to found a mutation in the BMPR1A gene. Sequencing of an additional 17 FCCX families resulted in a BMPR1A mutation frequency of 2/18 families (11%). Clarification of the mechanisms of the differential tumor susceptibility in LS increases the understanding of gene and organ specific targets of MMR deficiency. While it is generally accepted that widespread MMR deficiency and consequent microsatellite instability (MSI) drives tumorigenesis in LS, the timing of molecular alterations is controversial. In particular, it is important to know that alterations may occur several years before cancer formation, at stages that are still histologically regarded as normal. Identification of molecular markers that could predict the risk of malignant transformation may be used to improve surveillance and cancer prevention in genetically predisposed individuals. Significant fractions of families with colorectal and/or endometrial cancer presently lack molecular definition altogether. Our findings expand the phenotypic spectrum of BMPR1A mutations and, for the first time, link FCCX families to the germline mutation of a specific gene. In particular, our observations encourage screening of additional families with FCCX for BMPR1A mutation, which is necessary in obtaining a reliable estimate of the share of BMPR1A-associated cases among all FCCX families worldwide. Clinically, the identification of predisposing mutations enables targeted cancer prevention in proven mutation carriers and thereby reduces cancer morbidity and mortality in the respective families.

"Pitää kuitenkin lähentyä sitä vangin roolia, vaikka ite ois toista mieltä" : Diskurssianalyyttinen tutkimus toiseuden rakentumisesta vankilaopetuksessa

The focus of this discourse analytical study was to review the meanings which prison education and its participants are given in the formal educational policy and to find out whether these meanings are agreed by the prison students. The intrestes of this thesis were to examine what kind of social and individual promises are related to the prison education and what kind of subject positions are possible to the prison students. The thesis was also interested in the meanings of education in different contexts. The aim of this study was to examine prison education especially for women. This thesis was based on Michel Foucault s ideas of power and the view of this study was directly critical. The prison education was seen as normalizing governance which tends to prepare its subjects to the normal. In this process of differentiating the normal and the abnormal the subjects of prison education are reconstructed as the others . The three research questions of this thesis were: how and what kind of prison education is reconstructed firstly in the strategy of prison education and secondly in the interviews. Thirdly it was questioned how and what kind of meanings gender receive in the discourse of prison education. The main data was consisted by the Finnish Criminal Sanctions Agency s document The Strategy of the Prison education for years 2008 2012 and the three interviews of women who participated to prison education. The interviews were made for this thesis in Autumn 2010. Two other Finnish Criminal Sanctions Agency s documents Prisoners in education (2007) and Visible women (2008) - the report of the working group on female prisoners were also used as subtext materials. The methods of critical and realistic discourse analysis and rhetorical analysis were applied in the analysis. The results of the thesis support the outlook of prison education as a form of normalizing governance which reconstruct the others position for the prison students. Prison education was seen supportive for personal life control and for integrating to the society. The participants of prison education repeated the official discourses in their accounts which is a signal of internalized governance. The interviewees also used different types of anti-discourses when forming implications of prison education.

Pärjätäkseen pitää olla sosiaalinen, aktiivinen ja menestyvä ihminen. Kaikkea hyvää vaan heille, mutta entäs me muut? Vertaistuki Yksinäisyys-nettiryhmässä avunsaajan ja avunantajan näkökulmista.

Yksinäisyyden merkitys hyvinvointia uhkaavana tekijänä on viimeaikoina noussut esiin yhä enenevissä määrin. Yksinäiset korkeakouluopiskelijat ovat erityisen haavoittuvassa elämäntilanteessa, sillä nuoren aikuisen elämään liittyvät erityiset kehitykselliset haasteet. Tärkeää on, että opiskelijat saavat tukea tilanteeseensa, jotta yksinäisyyden kauaskantoisilta vaikutuksilta vältyttäisiin. Vertaistuki voi monen kohdalla olla tärkeää, ja Internet mahdollistaa matalan kynnyksen paikan avun hakemiseen. Tutkielmassani perehdyn Nyyti ry:n ylläpitämään, korkeakouluopiskelijoille tarkoitettuun Yksinäisyys-nettiryhmään, ja siinä esiintyvään vertaistukeen. Erityisen tutkimusasetelmastani tekee vertaistuen tarkastelu sen kaksijakoisuuden kautta: millaisia avunsaajana olemisen ja avunantajana toimimisen tapoja kirjoituksista on löydettävissä, ja miten ne suhteutuvat toisiinsa. Näin voidaan ymmärtää paremmin keskustelijoiden tarpeita ja odotuksia, ja sitä, miten ryhmä pystyy niihin vastaamaan. Aineistoa on tutkittu sisällönanalyysin menetelmin. Näyttäisi siltä, että ryhmään kohdistetaan enemmän odotuksia ja tarpeita kuin mihin se pystyy vastaamaan. Avunsaajana olemisen luokkia oli yhteensä 15, jotka kuvasivat viittä eri ulottuvuutta. Ulottuvuudet olivat kokemuksellisuus, kontrolliodotus, vaikeusaste, suhde tietoon ja odotuksellisuus. Avunantajana toimimisen kohdalla luokkia muodostui kahdeksan, jotka kuvasivat neljää ulottuvuutta. Näitä olivat empatia, eteenpäin suuntaavuus, opastus ja kyseenalaistus. Avunsaajana oleminen hallitsi nettiryhmän keskusteluja, ja sitä kuvastavat tekstit olivat paitsi määrällisesti pidempiä, myös sisällöllisesti rikkaampia. Suhteutettaessa avunsaajan ja avunantajan tapoja toisiinsa havaitaan, että ryhmässä osoitettu tuki pystyy hyvin vastaamaan moniin odotuksiin, mutta toisaalta jokin tuenmuoto saattaa olla päinvastainenkin joidenkin luokkien tarpeille. Voikin olla, että vertaistuesta on keskustelijoille hyötyä tiettyyn tasoon asti, mutta suuri määrä erilaisia tarpeita ja odotuksia tekee mahdottomaksi niihin kaikkiin vastaamisen. Hyvä jatkotutkimuksen aihe olisi haastatteluin selvittää kirjoittajien omia näkemyksiä siitä, mistä kokevat ryhmään kirjoittaessaan hyötyvänsä. Tutkielman keskeisimpiä lähteitä ovat olleet: Weiss, R.S. (1973). Loneliness: the experience of emotional and social isolation, Kraut, R. ym (1998). Internet paradox. A social technology that reduces social involvement and psychological well-being?, Jung, J. (1987) Toward a social psychology of social support., Dennis, C-L. (2003). Peer support within a health care context: a concept analysis.

Impact of pit-toilet leachate on groundwater chemistry and role of vadose zone in removal of nitrate and E-coli pollutants in Kolar District, Karnataka, India

Assessment of chemistry of groundwater infiltrated by pit-toilet leachate and contaminant removal by vadose zone form the focus of this study. The study area is Mulbagal Town in Karnataka State, India. Groundwater level measurements and estimation of unsaturated permeability indicated that the leachate recharged the groundwater inside the town at the rate of 1 m/day. The average nitrate concentration of groundwater inside the town (148 mg/L) was three times larger than the permissible limit (45 mg/L), while the average nitrate concentration of groundwater outside the town (30 mg/L) was below the permissible limit. The groundwater inside the town exhibited E. coli contamination, while groundwater outside the town was free of pathogen contamination. Infiltration of alkalis (Na+, K+) and strong acids (Cl-, SO4 (2-)) caused the mixed Ca-Mg-Cl type (60 %) and Na-Cl type (28 %) facies to predominate groundwater inside the town, while, Ca-HCO3 (35 %), mixed Ca-Mg-Cl type (35 %) and mixed Ca-Na-HCO3 type (28 %) facies predominated groundwater outside/periphery of town. Reductions in E. coli and nitrate concentrations with vadose zone thickness indicated its participation in contaminant removal. A 4-m thickness of unsaturated sand + soft, disintegrated weathered rock deposit facilitates the removal of 1 log of E. coli pathogen. The anoxic conditions prevailing in the deeper layers of the vadose zone (> 19 m thickness) favor denitrification resulting in lower nitrate concentrations (28-96 mg/L) in deeper water tables (located at depths of -29 to -39 m).

Sensory-organ-like response determines the magnetism of zigzag-edged honeycomb nanoribbons

We present an analytical effective theory for the magnetic phase diagram for zigzag-edge terminated honeycomb nanoribbons described by a Hubbard model with an interaction parameter U. We show that the edge magnetic moment varies as ln U and uncover its dependence on the width W of the ribbon. The physics of this owes its origin to the sensory-organ-like response of the nanoribbons, demonstrating that considerations beyond the usual Stoner-Landau theory are necessary to understand the magnetism of these systems. A first-order magnetic transition from an antiparallel orientation of the moments on opposite edges to a parallel orientation occurs upon doping with holes or electrons. The critical doping for this transition is shown to depend inversely on the width of the ribbon. Using variational Monte Carlo calculations, we show that magnetism is robust to fluctuations. Additionally, we show that the magnetic phase diagram is generic to zigzag-edge terminated nanostructures such as nanodots. Furthermore, we perform first-principles modeling to show how such magnetic transitions can be realized in substituted graphene nanoribbons. DOI: 10.1103/PhysRevB.87.085412

Estimate of N2O release from pit-toilets

The use of pit-toilets has severely contaminated the groundwater with nitrate ions in Mulbagal town, Karnataka, India. This paper examines the potential of nitrate ions in the pit-toilet effluents to transform to N2O and to escape to atmosphere from 16 wards of Mulbagal town. Anaerobic conditions prevailing in the pit-toilet convert 25 % of the available N to ammonium ions. Only 3-33 % of ammonium ions transform to nitrate ions in the pit-toilet and escape with the effluent. During migration to aquifer, only 4.5 % of available nitrate concentration in the effluent transforms to N-2 and N2O gases in the 1.5-m-thick saturated zone underlying the pit-toilet; 36-55 % of the gases comprise N2O and the remainder of N-2. Further only 18 % of N2O formed escapes to atmosphere, while the remainder is retained in soil solution. Calculations show that 9.88 x 10(13) molecules of N2O/cm(2) would be cumulatively released from 16 wards of Mulbagal town, over an area of 4.9 km(2).

Development of an ex vivo organ culture model using human gastro-intestinal tissue and Campylobacter jejuni.

Campylobacter jejuni is an important food-borne pathogen. However, relatively little is understood regarding its pathogenesis, and research is hampered by the lack of a suitable model. Recently, a number of groups have developed assays to study the pathogenic mechanisms of C. jejuni using cell culture models. Here, we report the development of an ex vivo organ culture model, allowing for the maintenance of intestinal mucosal tissue, to permit more complex host-bacterium interactions to be studied. Ex vivo organ culture highlights the propensity for C. jejuni to adhere to mucosal tissue via the flagellum, either as discrete colonies or as multicellular units.

Length-weight relationship and organ indices of pond raised and wild population of C. gariepinus (Burchell 1822) pisces-Claridae

Samples of C. gariepinus collected from the wild and cultured populations in Plateau and Niger States of Nigeria were analyzed for length-weight relationship and organ indices (Gonadosomatic index (GSI), hepatosomatic index (HSI), renalsomatic index (RSI) and somatic fat deposit index (PDI). High correlation and linear relationship between body length and body weight was observed in all sample population (P<0.05). A significant difference was observed between the GSI of males and females of both wild and cultured population and also between females of the wild and cultured population,(P < 0.05).There was no significant difference in HSI, CSI RSI and PDI of all the sample populations (P < 0.05).The importance of length-weight relationship and organ indices in fish production are discussed

Dynamic readout of subdiffraction-limited pit arrays with a silver superlens

Recent theoretical and experimental results suggested that the silver superlens could be constructed through controlling silver thin film thickness and preparation conditions, and applied in subdiffraction-limited optical imaging and optical lithography. In this work, we report another significant application of silver superlens-ultrahigh density optical data storage. With the silver superlens the subdiffraction-limited pit arrays on an optical disk are dynamically read out and the carrier-to-noise ratio can reach 25 dB for the thin film thickness of 46 nm. The readout laser power and readout velocity have little effect on the carrier-to-noise ratio. Additionally, in our experiment the silver thin film thickness needs to be controlled in the range from 20 to 80 nm.

On the dynamic readout of sub-diffraction-limit pit arrays with a silver thin film

Fast moving arrays of periodic sub-diffraction-limit pits were dynamically read out via a silver thin film. The mechanism of the dynamic readout is analysed and discussed in detail, both experimentally and theoretically. The analysis and experiment show that, in the course of readout, surface plasmons can be excited at the silver/air interface by the focused laser beam and amplified by the silver thin film. The surface plasmons are transmitted into the substrate/silver interface with a large enhancement. The surface waves at the substrate/silver interface are scattered by the sinusoidal pits of sub-diffraction-limit size. The scattered waves are collected by a converging lens and guided into the detector for the readout.

Geomicrobiology of meromictic, metal-mine pit lakes in the Iberian Pyrite Belt and biotechnological applications

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An epizootic of infectious hepatopancreatic and lymphoid organ necrosis disease in cultured Penaeus monodon: a case study

Shrimp disease of viral origin have caused large production losses worldwide. This paper presents a case study of shrimp (Penaeus monodon; Penaeus indicus) epizootic disease, covering an area of 1,050 ha in Andhra Pradesh, India. The disease struck shrimp farms in the area in July 1994. Samples from 26 shrimp farms were studied in the laboratory, and the pattern of the disease and of mortality recorded. The disease was classified as infectious hepatopancreatic and lymphoid organ necrosis disease (IHLN).