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Sample records for indian reservation mi

  1. Intestinal parasites among Yanomâmi indians

    OpenAIRE

    Confalonieri, U. E.; Araújo, A. J.; Ferreira, L. F.

    1989-01-01

    The findings of intestinal helminths and protozoans parasites from the Yanomâmi indians of the Roraima State in Brazil are reported. The fecal samples were collected before these communities started a permanent contact with non-indians. Comments are made on the possible ecological and evolutionary factors responsible for the patterns of parasitism observed.

  2. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Paramasivam Prabu

    Full Text Available Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM. While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT, impaired glucose tolerance (IGT and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  3. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  4. 77 FR 42326 - Renewal of Agency Information Collection for Indian Reservation Roads

    Science.gov (United States)

    2012-07-18

    ... Indian Reservation Roads AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of submission to OMB... information for Indian Reservation Roads. The information collection is currently authorized by OMB Control... recognized Tribal governments to participate in the Indian Reservation Roads (IRR) program as defined in 25 U...

  5. 77 FR 14465 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Science.gov (United States)

    2012-03-09

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Public Transportation on Indian... in funding provided by the Public Transportation on Indian Reservations Program (Tribal Transit... establishing the Public Transportation on Indian Reservations Program (Tribal Transit Program or TTP). This...

  6. The Changing Role of the Chief on a California Indian Reservation.

    Science.gov (United States)

    Miller, Virginia P.

    1989-01-01

    Discusses the Yuki Indian chief's aboriginal role as leader, decision maker, and group coordinator and how that role, revived by Indian agents, served acculturation forces when the Yuki became reservation Indians. Describes how chiefs, relatively progressive and acculturated individuals, were effective middlemen between the agents and Indians.…

  7. 25 CFR 170.120 - What restrictions apply to the use of an Indian Reservation Road?

    Science.gov (United States)

    2010-04-01

    ... Reservation Road? 170.120 Section 170.120 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and Eligibility Use of Irr and Cultural Access Roads § 170.120 What restrictions apply to the use of an Indian...

  8. Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians—an ethnic population characterized to represent ‘Asian Indian phenotype’ known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a ‘New Lead’ in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes. PMID:26020947

  9. 77 FR 24975 - Renewal of Agency Information Collection for Indian Reservation Roads; Request for Comments

    Science.gov (United States)

    2012-04-26

    ... Indian Reservation Roads; Request for Comments AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice...) approval for the collection of information for Indian Reservation Roads. The information collection is... recognized Tribal governments to participate in the Indian Reservation Roads (IRR) program as defined in 25 U...

  10. 77 FR 67439 - Fiscal Year 2013 Public Transportation on Indian Reservations Program

    Science.gov (United States)

    2012-11-09

    ... Year 2013 Public Transportation on Indian Reservations Program AGENCY: Federal Transit Administration... changes in the Public Transportation on Indian Reservations program (Tribal Transit Program) in accordance... Public Meeting: FTA will provide outreach in conjunction with the National Tribal Transportation...

  11. 78 FR 27284 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Science.gov (United States)

    2013-05-09

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Public Transportation on Indian... Federal Register Notice (77 FR 67439) Fiscal Year 2013 Public Transportation on Indian Reservation Program... formula apportionment to eligible Indian tribes providing public transportation on tribal lands. FTA...

  12. 76 FR 2409 - Proclaiming Certain Lands, Lot 32 Acquisition, as an Addition to the Bay Mills Indian Reservation...

    Science.gov (United States)

    2011-01-13

    ..., as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan..., more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community of... Mills Indian Reservation and part of the Bay Mills Indian Community of Michigan for the exclusive use of...

  13. B.C. Indians Living Off Reserve: Some Economic Aspects.

    Science.gov (United States)

    Stanbury, W. T.

    The study examined the economic development of British Columbia (B.C.) Indians who have moved off-reserve. The discussion included: (1) obtaining the sample, (2) sample description, (3) reasons for living off-reserve, (4) employment opportunities, (5) income and poverty line, and (6) academic achievement. A total of 1,095 persons interviewed…

  14. 77 FR 547 - Fiscal Year 2011 Public Transportation on Indian Reservations Program Project Selections

    Science.gov (United States)

    2012-01-05

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Fiscal Year 2011 Public Transportation... 5311 (c), Public Transportation on Indian Reservations program funds in support of the Tribal Transit... for public transportation services on and around Indian reservations. FOR FURTHER INFORMATION CONTACT...

  15. 76 FR 44394 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Science.gov (United States)

    2011-07-25

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Public Transportation on Indian... the Public Transportation on Indian Reservations Program (Tribal Transit Program) (TTP). This program... of the Census and may be used for public transportation capital projects, operating costs of...

  16. 76 FR 56786 - Renewal of Agency Information Collection for Law and Order on Indian Reservations-Marriage...

    Science.gov (United States)

    2011-09-14

    ... Law and Order on Indian Reservations--Marriage & Dissolution Applications; Request for Comments AGENCY... on Indian Reservations--Marriage & Dissolution Applications, which concerns marriage and dissolution of a marriage in a Court of Indian Offenses. The information collection is currently authorized by...

  17. 76 FR 80387 - Renewal of Agency Information Collection for Law and Order on Indian Reservations-Marriage...

    Science.gov (United States)

    2011-12-23

    ... Law and Order on Indian Reservations--Marriage & Dissolution Applications; Request for Comments... ``Law and Order on Indian Reservations--Marriage & Dissolution Applications.'' The information... personal information necessary for a Court of Indian Offenses to issue a marriage license or dissolve a...

  18. 75 FR 27114 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Science.gov (United States)

    2010-05-13

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Public Transportation on Indian..., 2005)] amended 49 U.S.C. 5311(c) by establishing the Public Transportation on Indian Reservations... Census and may be used for public transportation capital projects, operating costs of equipment and...

  19. Hydrogeology and ground-water quality of glacial-drift aquifers, Leech Lake Indian Reservation, north-central Minnesota

    Science.gov (United States)

    Lindgren, R.J.

    1996-01-01

    Among the duties of the water managers of the Leech Lake Indian Reservation in north-central Minnesota are the development and protection of the water resources of the Reservation. The U.S. Geological Survey, in cooperation with the Leech Lake Indian Reservation Business Committee, conducted a three and one half-year study (1988-91) of the ground-water resources of the Leech Lake Indian Reservation. The objectives of this study were to describe the availability and quality of ground water contained in glacial-drift aquifers underlying the Reservation.

  20. Spatial heterogeneity of malaria in Indian reserves of Southwestern Amazonia, Brazil

    Directory of Open Access Journals (Sweden)

    Santos Ricardo

    2008-11-01

    Full Text Available Abstract Background Malaria constitutes a major cause of morbidity in the Brazilian Amazon where an estimated 6 million people are considered at high risk of transmission. Indigenous peoples in the Amazon are particularly vulnerable to potentially epidemic disease such as malaria; notwithstanding, very little is known about the epidemiology of malaria in Indian reservations of the region. The aim of this paper is to present a spatial analysis of malaria cases over a four-year time period (2003–2006 among indigenous peoples of the Brazilian State of Rondônia, southwestern Amazon, by using passive morbidity data (results from Giemsa-stained thick blood smears gathered from the National Malaria Epidemiologic Surveillance System databank. Results A total of 4,160 cases of malaria were recorded in 14 Indian reserves in the State of Rondônia between 2003 and 2006. In six reservations no cases of malaria were reported in the period. Overall, P. vivax accounted for 76.18 of malaria cases reported in the indigenous population of Rondônia. The P. vivax/P. falciparum ratio for the period was 3.78. Two reserves accounted for over half of the cases reported for the total indigenous population in the period – Roosevelt and Pacaas Novas – with a total of 1,646 (39.57% and 1,145 (27.52% cases, respectively. Kernel mapping of malaria mean Annual Parasite Index – API according to indigenous reserves and environmental zones revealed a heterogeneous pattern of disease distribution, with one clear area of high risk of transmission comprising reservations of west Rondônia along the Guaporé-Madeira River basins, and another high risk area to the east, on the Roosevelt reserve. Conclusion By means of kernel mapping, it was shown that malaria risk varies widely between Indian reserves and environmental zones defined on the basis of predominant ecologic characteristics and land use patterns observed in the southwestern Brazilian Amazon. The geographical

  1. 77 FR 54607 - Proclaiming Certain Lands, Sugar Parcel Lands, as an Addition to the Bay Mills Indian Reservation...

    Science.gov (United States)

    2012-09-05

    ..., as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan... acres, more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  2. 77 FR 54607 - Proclaiming Certain Lands, Dafter Parcel, as an Addition to the Bay Mills Indian Reservation for...

    Science.gov (United States)

    2012-09-05

    ... an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan AGENCY..., more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community of... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  3. 75 FR 40849 - Implementation of Question 10 of 25 CFR Part 170, Subpart C, Indian Reservation Roads Program

    Science.gov (United States)

    2010-07-14

    ... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Implementation of Question 10 of 25 CFR Part 170, Subpart C, Indian Reservation Roads Program AGENCY: Bureau of Indian Affairs, Interior. [[Page... Distribution Factor (RNDF) formula for Indian Reservation Road (IRR) Program funds. The determination is...

  4. Tax Avoidance and Evasion: Cigarette Purchases From Indian Reservations Among US Adult Smokers, 2010-2011

    Science.gov (United States)

    Xu, Xin; Tynan, Michael A.; Gerzoff, Robert B.; Caraballo, Ralph S.; Promoff, Gabbi R.

    2017-01-01

    Excise taxes are the primary public health strategy used to increase the price of cigarettes in the United States. Rather than quitting or reducing consumption of cigarettes, some price-sensitive smokers may avoid state and local excise taxes by purchasing cigarettes from Indian reservations. The objectives of this study were to (1) provide the most recent state-specific prevalence of purchases made on Indian reservations by non–American Indians/Alaska Natives (non-AI/ANs) and (2) assess the impact of these purchases on state tax revenues. We used data from a large national and state-representative survey, the 2010-2011 Tobacco Use Supplement to the Current Population Survey, which collects self-reported measures on cigarette use and purchases. Nationwide, 3.8% of non-AI/AN smokers reported purchasing cigarettes from Indian reservations. However, in Arizona, Nevada, New Mexico, New York, Oklahoma, and Washington State, about 15% to 30% of smokers reported making such purchases, resulting in annual tax revenue losses ranging from $3.5 million (Washington State) to $292 million (New York) during 2010-2011. Strategies to reduce the sale of non- or lower-taxed cigarettes to non-AI/ANs on Indian reservations have the potential to decrease smoking prevalence and recoup lost revenue from purchases made on reservations. PMID:28395142

  5. Tax Avoidance and Evasion: Cigarette Purchases From Indian Reservations Among US Adult Smokers, 2010-2011.

    Science.gov (United States)

    Wang, Xu; Xu, Xin; Tynan, Michael A; Gerzoff, Robert B; Caraballo, Ralph S; Promoff, Gabbi R

    Excise taxes are the primary public health strategy used to increase the price of cigarettes in the United States. Rather than quitting or reducing consumption of cigarettes, some price-sensitive smokers may avoid state and local excise taxes by purchasing cigarettes from Indian reservations. The objectives of this study were to (1) provide the most recent state-specific prevalence of purchases made on Indian reservations by non-American Indians/Alaska Natives (non-AI/ANs) and (2) assess the impact of these purchases on state tax revenues. We used data from a large national and state-representative survey, the 2010-2011 Tobacco Use Supplement to the Current Population Survey, which collects self-reported measures on cigarette use and purchases. Nationwide, 3.8% of non-AI/AN smokers reported purchasing cigarettes from Indian reservations. However, in Arizona, Nevada, New Mexico, New York, Oklahoma, and Washington State, about 15% to 30% of smokers reported making such purchases, resulting in annual tax revenue losses ranging from $3.5 million (Washington State) to $292 million (New York) during 2010-2011. Strategies to reduce the sale of non- or lower-taxed cigarettes to non-AI/ANs on Indian reservations have the potential to decrease smoking prevalence and recoup lost revenue from purchases made on reservations.

  6. 40 CFR 131.35 - Colville Confederated Tribes Indian Reservation.

    Science.gov (United States)

    2010-07-01

    ..., springs, seeps and wetlands. (15) Temperature means water temperature expressed in Centigrade degrees (C... used. (f) General water use and criteria classes. The following criteria shall apply to the various classes of surface waters on the Colville Indian Reservation: (1) Class I (Extraordinary)—(i) Designated...

  7. Rickettsia bellii, Rickettsia amblyommii, and Laguna Negra hantavirus in an Indian reserve in the Brazilian Amazon.

    Science.gov (United States)

    de Barros Lopes, Lívia; Guterres, Alexandro; Rozental, Tatiana; Carvalho de Oliveira, Renata; Mares-Guia, Maria Angélica; Fernandes, Jorlan; Figueredo, José Ferreira; Anschau, Inês; de Jesus, Sebastião; V Almeida, Ana Beatriz M; Cristina da Silva, Valéria; Gomes de Melo Via, Alba Valéria; Bonvicino, Cibele Rodrigues; D'Andrea, Paulo Sérgio; Barreira, Jairo Dias; Sampaio de Lemos, Elba Regina

    2014-04-17

    The purpose of this study was to identify the presence of rickettsia and hantavirus in wild rodents and arthropods in response to an outbreak of acute unidentified febrile illness among Indians in the Halataikwa Indian Reserve, northwest of the Mato Grosso state, in the Brazilian Amazon. Where previously surveillance data showed serologic evidence of rickettsia and hantavirus human infection. The arthropods were collected from the healthy Indian population and by flagging vegetation in grassland or woodland along the peridomestic environment of the Indian reserve. Wild rodents were live-trapped in an area bordering the reserve limits, due the impossibility of capturing wild animals in the Indian reserve. The wild rodents were identified based on external and cranial morphology and karyotype. DNA was extracted from spleen or liver samples of rodents and from invertebrate (tick and louse) pools, and the molecular characterization of the rickettsia was through PCR and DNA sequencing of fragments of two rickettsial genes (gltA and ompA). In relation to hantavirus, rodent serum samples were serologically screened by IgG ELISA using the Araraquara-N antigen and total RNA was extracted from lung samples of IgG-positive rodents. The amplification of the complete S segment was performed. A total of 153 wild rodents, 121 louse, and 36 tick specimens were collected in 2010. Laguna Negra hantavirus was identified in Calomys callidus rodents and Rickettsia bellii, Rickettsia amblyommii were identified in Amblyomma cajennense ticks. Zoonotic diseases such as HCPS and spotted fever rickettsiosis are a public health threat and should be considered in outbreaks and acute febrile illnesses among Indian populations. The presence of the genome of rickettsias and hantavirus in animals in this Indian reserve reinforces the need to include these infectious agents in outbreak investigations of febrile cases in Indian populations.

  8. Population Growth and Sprawl on the Pine Ridge Indian Reservation, South Dakota

    Science.gov (United States)

    Campbell, R. L.

    2006-05-01

    The most important impact on global land cover is human use and development. With the recent population growth occurring on the reservations in South Dakota, especially Pine Ridge Indian Reservation, the towns and agricultural areas of the reservation are undergoing a change. Although urban sprawl certainly is not a consideration on the reservations, the population explosion currently underway has seen a subsequent increase in rural sprawl. In this case, rural sprawl is defined as exponential population growth and geographic expansion of remote reservation communities. Using satellite imagery and software to render these images is a cost effective way to investigate this growth. Also, using remotely sensed data and a GIS (geographic information system) package can address different issues that concern people and communities in and around the Pine Ridge area. The objective of my project is to observe land use change on the Pine Ridge Indian reservation using Geographic Information Systems such as; ARCGis 9, ENVI, and Multispec, along with Landsat 4, 5, and 7 imagery over the past 20 years.

  9. GREYBULL SANDSTONE PETROLEUM POTENTIAL ON THE CROW INDIAN RESERVATION, SOUTH-CENTRAL MONTANA

    Energy Technology Data Exchange (ETDEWEB)

    David A. Lopez

    2000-12-14

    Evaluation of the Lower Cretaceous Greybull Sandstone on the Crow Indian Reservation for potential stratigraphic traps in the valley-fill sandstone was the focus of this project. The Crow Reservation area, located in south-central Montana, is part of the Rocky Mountain Foreland structural province, which is characterized by Laramide uplifts and intervening structural basins. The Pryor and Bighorn mountains, like other foreland uplifts, are characterized by asymmetrical folds associated with basement-involved reverse faults. The reservation area east of the mountains is on the northwestern flank of the Powder River Basin. Therefore, regional dips are eastward and southeastward; however, several prominent structural features interrupt these regional dips. The nearly 4,000 mi{sup 2} reservation is under explored but has strong potential for increased oil and gas development. Oil and gas production is well established in the Powder River Basin of Wyoming to the south as well as in the areas north and west of the reservation. However, only limited petroleum production has been established within the reservation. Geologic relations and trends indicate strong potential for oil and gas accumulations, but drilling has been insufficient for their discovery. The Greybull Sandstone, which is part of the transgressive systems tract that includes the overlying Fall River Sandstone, was deposited on a major regional unconformity. The erosional surface at the base of the Greybull Sandstone is the +100 Ma, late Aptian-Early Albian regional unconformity of Weimer (1984). This lowstand erosional surface was controlled by a basin-wide drop in sea level. In areas where incised Greybull channels are absent, the lowstand erosional unconformity is at the base of the Fall River Sandstone and equivalent formations. During the pre-Greybull lowstand, sediment bypassed this region. In the subsequent marine transgression, streams began to aggrade and deposit sand of the lower Greybull Sandstone

  10. miRNAting control of DNA methylation

    Indian Academy of Sciences (India)

    miRNAting control of DNA methylation. ASHWANI ... function and biological process ... Enrichment analysis of the genes methylated by DRM2 for molecular function and biological ... 39(3), June 2014, 365–380, © Indian Academy of Sciences.

  11. 75 FR 30430 - Notice Terminating the Exclusion of Indian Tribal Leases in the Uintah and Ouray Reservation From...

    Science.gov (United States)

    2010-06-01

    .... Lessees must value gas production from Ute Indian tribal leases on the Reservation with the index-based... Mountain Index Zone to determine the index zone price; or lessees may obtain the index-based values from..., based on a request by the Ute Indian Tribe of the Uintah and Ouray Reservation. DATES: Effective Date...

  12. ARMOUR – A Rice miRNA: mRNA Interaction Resource

    OpenAIRE

    Neeti Sanan-Mishra; Anita Tripathi; Kavita Goswami; Rohit N. Shukla; Madavan Vasudevan; Hitesh Goswami

    2018-01-01

    ARMOUR was developed as ARice miRNA:mRNA interaction resource. This informative and interactive database includes the experimentally validated expression profiles of miRNAs under different developmental and abiotic stress conditions across seven Indian rice cultivars. This comprehensive database covers 689 known and 1664 predicted novel miRNAs and their expression profiles in more than 38 different tissues or conditions along with their predicted/known target transcripts. The understanding of...

  13. Rickettsia bellii, Rickettsia amblyommii, and Laguna Negra hantavirus in an Indian reserve in the Brazilian Amazon

    OpenAIRE

    de Barros Lopes, Lívia; Guterres, Alexandro; Rozental, Tatiana; Carvalho de Oliveira, Renata; Mares-Guia, Maria Angélica; Fernandes, Jorlan; Figueredo, José Ferreira; Anschau, Inês; de Jesus, Sebastião; V Almeida, Ana Beatriz M; Cristina da Silva, Valéria; Gomes de Melo Via, Alba Valéria; Bonvicino, Cibele Rodrigues; D’Andrea, Paulo Sérgio; Barreira, Jairo Dias

    2014-01-01

    Background The purpose of this study was to identify the presence of rickettsia and hantavirus in wild rodents and arthropods in response to an outbreak of acute unidentified febrile illness among Indians in the Halataikwa Indian Reserve, northwest of the Mato Grosso state, in the Brazilian Amazon. Where previously surveillance data showed serologic evidence of rickettsia and hantavirus human infection. Methods The arthropods were collected from the healthy Indian population and by flagging v...

  14. Ethnicity as a determinant of ovarian reserve: differences in ovarian aging between Spanish and Indian women.

    Science.gov (United States)

    Iglesias, Carlos; Banker, Manish; Mahajan, Nalini; Herrero, Leyre; Meseguer, Marcos; Garcia-Velasco, Juan A

    2014-07-01

    To investigate differences in ovarian reserve markers (antimüllerian hormone [AMH] and antral follicle count [AFC]) in Indian and Spanish women. Cross-sectional study. In vitro fertilization (IVF) clinics. Infertile Spanish (n=229) and Indian (n=236) women who underwent controlled ovarian stimulation for IVF from January to October 2012. None. Data on ovarian reserve markers and results after ovarian stimulation were collected. The mean age of women undergoing their first or second IVF cycle was significantly higher in Spanish than in Indian women (37.5±3.3 years vs. 31.5±3.8 years). Despite this 6-year age gap, AFCs were similar (9.5±4.7 vs. 9.9±4.6), as were day 3 FSH levels (7.5±4.5 IU/L vs. 6.9±2.3 IU/L). AMH levels were slightly lower in Spanish women (1.6±1.7 ng/mL vs. 2.5±1.6 ng/mL). Multivariate regression analysis showed that being Indian decreased AFC by 2.3, such that AFC in Indian women was similar to that in Spanish women 6.3 years older (95% confidence interval 3.39-1.10). Similar ovarian reserve markers and ovarian response were observed in women with a 6-year age difference in favor of the Spanish, suggesting ethnic differences in ovarian aging. Further research is needed to understand whether these differences are genetically induced or are caused by other variables, such as nutrition. Our results may help clinicians to counsel infertile women when discussing assisted reproductive technology outcomes according to age and ethnic background. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Shigellosis on Indian reserves in Manitoba, Canada: its relationship to crowded housing, lack of running water, and inadequate sewage disposal.

    Science.gov (United States)

    Rosenberg, T; Kendall, O; Blanchard, J; Martel, S; Wakelin, C; Fast, M

    1997-09-01

    This study compares incidence and hospitalization rates for shigellosis between Indians and the rest of the population in Manitoba, Canada. It examines the relationship between shigellosis and environmental conditions on reserves. Rates were calculated with surveillance data and a survey of environmental infrastructure was done. Indians had shigellosis incidence and hospitalization rates that were 29 and 12 times as high, respectively, as those of the rest of the population. Household crowding, lack of piped water, and inadequate sewage disposal were significantly associated with an increased incidence of shigellosis on reserves. Many cases of shigellosis may be prevented by improving living conditions on Indian reserves.

  16. 78 FR 1301 - Fiscal Year 2012 Public Transportation on Indian Reservations Program Project Selections

    Science.gov (United States)

    2013-01-08

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Fiscal Year 2012 Public Transportation... Affairs (BIA) in the U.S. Department of the Interior for public transportation. An additional $500,000 is... Fiscal Year 2013 Public Transportation on Indian Reservations Program, which: (1) Introduces FTA's...

  17. 77 FR 26785 - Implementation of Indian Reservation Roads Program and Streamlining the Federal Delivery of...

    Science.gov (United States)

    2012-05-07

    ... Highway Administration (FHWA) will also present an update on legislation involving the Indian Reservation......... 9 a.m.-4:30 p.m. June 7, 2012 Spokane, WA........ 9 a.m.-4:30 p.m. June 12, 2012 Albuquerque, NM...

  18. 77 FR 36289 - Implementation of Indian Reservation Roads Program and Streamlining the Federal Delivery of...

    Science.gov (United States)

    2012-06-18

    ... reauthorization of the current transportation legislation involving the Indian Reservation Roads program or, if new transportation legislation is enacted prior to the meetings, BIA and FHWA will discuss its... Spokane, WA..... 9 a.m.-4:30 p.m. June 12, 2012 Albuquerque, NM. 9 a.m.-4:30 p.m. June 13, 2012 Phoenix...

  19. Water resources of the Santa Ysabel and Mesa Grande Indian Reservations, San Diego County, California

    Science.gov (United States)

    Freckleton, John R.

    1981-01-01

    The Santa Ysabel (consisting of three tracts) and Mesa Grande Indian Reservations are in north-central San Diego County, Calif. On both reservations fractured and weathered igneous and metamorphic rocks and alluvium are water bearing; however, no wells are known to derive their water entirely from alluvium. Well yields range from 2.5 to 250 gallons per minute. Springs occur where saturated fractured or weathered material intersects the land surface. Spring discharge ranged from 0 gallon per minute (November 1979) to 9.4 gallons per minute (November 1979). Few data are available for the surface water characteristics of the study area. One-time measurements of discharge at selected stream sites were made in late November 1979 and late May 1980; discharges ranged from less than 0.01 cubic foot per second to an estimated 3 cubic feet per second. Further study of the surface-water systems would provide a basis for estimating their development potential. The existing water-supply development on the Santa Ysabel Indian Reservation is adequate for the present residents. The Mesa Grande reservation was unoccupied in 1952, was reportedly unoccupied in November 1979, and has no developed water supply. Additional water can be developed for both reservations from the igneous and metamorphic rock, from presently undeveloped springs, and from perennial reaches of the larger streams. Except for excessive iron and sodium at some ground-water sites and excessive sodium at a few surface-water sites, the water is of suitable quality for domestic and agricultural use. (USGS)

  20. 25 CFR 63.5-63.9 - [Reserved

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false [Reserved] 63.5-63.9 Section 63.5-63.9 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Purpose, Policy, and Definitions §§ 63.5-63.9 [Reserved] ...

  1. Groundwater data collection for the Quinault Indian Nation, Grays Harbor and Jefferson Counties, Washington

    Science.gov (United States)

    Kahle, Sue C.; Fasser, Elisabeth T.; Olsen, Theresa D.

    2017-11-03

    Groundwater data were collected on the Quinault Indian Reservation to provide the Quinualt Indian Nation (QIN) with basic knowledge of the existing wells and springs on the reservation, and to establish a water-level network to be monitored by QIN to begin building a long-term groundwater dataset. The 327 mi2 Quinault Indian Reservation is located within the heavily forested Queets-Quinault watershed along the west-central coast of Washington and includes the coastal communities of Taholah and Queets, and the inland community of Amanda Park. Groundwater data were collected or compiled for 87 sites—82 wells and 5 springs. In October 2016, a field inventory was done to locate the sites and acquire site data. Groundwater levels were measured in 15 of the field-inventoried wells and 3 of those wells were observed as flowing (artesian). A monthly groundwater‑level monitoring network of 13 wells was established by the U.S. Geological Survey in March 2017, and the network was transferred to QIN in June 2017 for continued measurements.Several data needs were identified that would provide a more complete understanding of the groundwater system of the Quinault Indian Reservation. The collection of monthly water-level data for multiple years is an important first step in understanding seasonal and long term changes in water levels. Additionally, the collection of baseline groundwater chemistry and quality data across the reservation would help with future efforts to monitor existing and potentially changing groundwater quality conditions. Development of a water budget of the Queets-Quinault Watershed and the reservation within that area would provide water users with a better understanding of this important resource and provide needed information about the competing demands on local water sources.

  2. Search for <mi>CP> Violation and Measurement of the Branching Fraction in the Decay <mi>D>0<mi>KS>0<mi>KS>0

    Energy Technology Data Exchange (ETDEWEB)

    Dash, N.; Bahinipati, S.; Bhardwaj, V.; Trabelsi, K.; Adachi, I.; Aihara, H.; Al Said, S.; Asner, D. M.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Bansal, V.; Barberio, E.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bondar, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Breibeck, F.; Browder, T. E.; Červenkov, D.; Chang, M. -C.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Cho, K.; Choi, Y.; Cinabro, D.; Di Carlo, S.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Epifanov, D.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Gillard, R.; Goldenzweig, P.; Haba, J.; Hara, T.; Hayasaka, K.; Hayashii, H.; Hedges, M. T.; Hou, W. -S.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jacobs, W. W.; Jaegle, I.; Jeon, H. B.; Jin, Y.; Joffe, D.; Joo, K. K.; Julius, T.; Kahn, J.; Kaliyar, A. B.; Karyan, G.; Katrenko, P.; Kawasaki, T.; Kiesling, C.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kinoshita, K.; Kodyš, P.; Korpar, S.; Kotchetkov, D.; Križan, P.; Krokovny, P.; Kuhr, T.; Kulasiri, R.; Kumar, R.; Kumita, T.; Kuzmin, A.; Kwon, Y. -J.; Lange, J. S.; Lee, I. S.; Li, C. H.; Li, L.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matvienko, D.; Merola, M.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, S.; Moon, H. K.; Mori, T.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K. J.; Natkaniec, Z.; Nayak, M.; Niiyama, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Ono, H.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Pardi, S.; Park, C. -S.; Park, H.; Paul, S.; Pedlar, T. K.; Pesántez, L.; Pestotnik, R.; Piilonen, L. E.; Prasanth, K.; Ritter, M.; Rostomyan, A.; Sahoo, H.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Schwartz, A. J.; Seino, Y.; Senyo, K.; Sevior, M. E.; Shebalin, V.; Shen, C. P.; Shibata, T. -A.; Shiu, J. -G.; Shwartz, B.; Simon, F.; Sokolov, A.; Solovieva, E.; Starič, M.; Strube, J. F.; Stypula, J.; Sumisawa, K.; Sumiyoshi, T.; Takizawa, M.; Tamponi, U.; Tanida, K.; Tenchini, F.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Vorobyev, V.; Vossen, A.; Waheed, E.; Wang, C. H.; Wang, M. -Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Widmann, E.; Williams, K. M.; Won, E.; Yamashita, Y.; Ye, H.; Yelton, J.; Yook, Y.; Yuan, C. Z.; Yusa, Y.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.

    2017-10-01

    We report a study of the decay <mi>D>0<mi>KS>0<mi>KS>0 using 921 fb-1 of data collected at or near the Υ(4S) and Υ(5S) resonances with the Belle detector at the KEKB asymmetric energy e+e- collider. The measured time-integrated CP asymmetry is ACP(<mi>D>0<mi>KS>0<mi>KS>0) = (-0.02 ± 1.53 ± 0.02 ± 0.17)%, and the branching fraction is B(<mi>D>0<mi>KS>0<mi>KS>0) = (1.321 ± 0.023 ± 0.036 ± 0.044) × 10-4, where the first uncertainty is statistical, the second is systematic, and the third is due to the normalization mode (<mi>D>0<mi>KS>0π0). These results are significantly more precise than previous measurements available for this mode. The ACP measurement is consistent with the standard model expectation.

  3. Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle.

    Science.gov (United States)

    Wang, Xing Ping; Luoreng, Zhuo Ma; Zan, Lin Sen; Raza, Sayed Haidar Abbas; Li, Feng; Li, Na; Liu, Shuan

    2016-10-01

    This study reports a significant up-regulation of bta-miR-146a and bta-miR-146b expression levels in bovine mammary tissues infected with subclinical, clinical and experimental mastitis. Potential target genes are involved in multiple immunological pathways. These results suggest a regulatory function of both miRNAs for the bovine inflammatory response in mammary tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Rural Sprawl and the Impact of Human Land Use on the Pine Ridge Indian Reservation, South Dakota

    Science.gov (United States)

    Campbell, R.; Bennett, T.

    2005-12-01

    The most important impact on global land cover is human use and development. With the recent population growth occurring on the reservations in South Dakota, specifically Pine Ridge Indian Reservation, the towns and communities of the reservation are undergoing change. Although urban sprawl certainly is not a consideration on the reservations, the population explosion currently underway has seen a subsequent increase in rural sprawl. In this case, rural sprawl is defined as exponential population growth and geographic expansion of remote reservation communities. The capacity of satellite imagery to encompass large land tracts make the use of this technology a cost effective way to visualize and investigate population growth in rural communities. Likewise, integrating remotely sensed data into a Geographic Information Systems (GIS) can be a powerful tool to identify environmental and other land use issues that impact the people and communities in and around the Pine Ridge area. The objective of this research is to (1) observe and calculate land cover change around three communities on the Pine Ridge Indian reservation using remotely sensed data (Landsat MSS, TM and ETM+) and Geographic Information Systems over a 20 year span, and (2) to discuss the potential impacts of rural sprawl on the Pine Ridge Reservation, SD. Preliminary results indicate that land cover has changed in relationship to increased population growth within three communities on the reservation. New housing developments, roads and buildings have appeared and these changes were detectable using Landsat imagery. These results will be discussed along with the experiences and education through the NASA Goddard Internship sponsored by the North Dakota Association of Tribal Colleges.

  5. Methylmercury risk and awareness among American Indian women of childbearing age living on an inland northwest reservation

    Energy Technology Data Exchange (ETDEWEB)

    Kuntz, Sandra W., E-mail: skuntz@montana.edu [Montana State University, College of Nursing, 32 Campus Drive 7416, Missoula, MT 59812-7416 (United States); Hill, Wade G. [Montana State University, Sherrick Hall, PO Box 173560, Bozeman, MT 59717-3560 (United States); Linkenbach, Jeff W.; Lande, Gary [Montana State University, Culbertson Hall, Bozeman, MT 59717-3560 (United States); Larsson, Laura [Montana State University, Sherrick Hall, PO Box 173560, Bozeman, MT 59717-3560 (United States)

    2009-08-15

    American Indian women and children may be the most overrepresented among the list of disparate populations exposed to methylmercury. American Indian people fish on home reservations where a state or tribal fishing license (a source of advisory messaging) is not required. The purpose of this study was to examine fish consumption, advisory awareness, and risk communication preferences among American Indian women of childbearing age living on an inland Northwest reservation. For this cross-sectional descriptive study, participants (N=65) attending a Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinic were surveyed between March and June 2006. An electronic questionnaire adapted from Anderson et al. (2004) was evaluated for cultural acceptability and appropriateness by tribal consultants. Regarding fish consumption, approximately half of the women surveyed (49%) indicated eating locally caught fish with the majority signifying they consumed medium- and large-size fish (75%) that could result in exposure to methylmercury. In addition, a serendipitous discovery indicated that an unanticipated route of exposure may be fish provided from a local food bank resulting from sportsman's donations. The majority of women (80%) were unaware of tribal or state fish advisory messages; the most favorable risk communication preference was information coming from doctors or healthcare providers (78%). Since the population consumes fish and has access to locally caught potentially contaminated fish, a biomonitoring study to determine actual exposure is warranted.

  6. Methylmercury risk and awareness among American Indian women of childbearing age living on an inland northwest reservation

    International Nuclear Information System (INIS)

    Kuntz, Sandra W.; Hill, Wade G.; Linkenbach, Jeff W.; Lande, Gary; Larsson, Laura

    2009-01-01

    American Indian women and children may be the most overrepresented among the list of disparate populations exposed to methylmercury. American Indian people fish on home reservations where a state or tribal fishing license (a source of advisory messaging) is not required. The purpose of this study was to examine fish consumption, advisory awareness, and risk communication preferences among American Indian women of childbearing age living on an inland Northwest reservation. For this cross-sectional descriptive study, participants (N=65) attending a Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinic were surveyed between March and June 2006. An electronic questionnaire adapted from Anderson et al. (2004) was evaluated for cultural acceptability and appropriateness by tribal consultants. Regarding fish consumption, approximately half of the women surveyed (49%) indicated eating locally caught fish with the majority signifying they consumed medium- and large-size fish (75%) that could result in exposure to methylmercury. In addition, a serendipitous discovery indicated that an unanticipated route of exposure may be fish provided from a local food bank resulting from sportsman's donations. The majority of women (80%) were unaware of tribal or state fish advisory messages; the most favorable risk communication preference was information coming from doctors or healthcare providers (78%). Since the population consumes fish and has access to locally caught potentially contaminated fish, a biomonitoring study to determine actual exposure is warranted.

  7. ARMOUR - A Rice miRNA: mRNA Interaction Resource.

    Science.gov (United States)

    Sanan-Mishra, Neeti; Tripathi, Anita; Goswami, Kavita; Shukla, Rohit N; Vasudevan, Madavan; Goswami, Hitesh

    2018-01-01

    ARMOUR was developed as A Rice miRNA:mRNA interaction resource. This informative and interactive database includes the experimentally validated expression profiles of miRNAs under different developmental and abiotic stress conditions across seven Indian rice cultivars. This comprehensive database covers 689 known and 1664 predicted novel miRNAs and their expression profiles in more than 38 different tissues or conditions along with their predicted/known target transcripts. The understanding of miRNA:mRNA interactome in regulation of functional cellular machinery is supported by the sequence information of the mature and hairpin structures. ARMOUR provides flexibility to users in querying the database using multiple ways like known gene identifiers, gene ontology identifiers, KEGG identifiers and also allows on the fly fold change analysis and sequence search query with inbuilt BLAST algorithm. ARMOUR database provides a cohesive platform for novel and mature miRNAs and their expression in different experimental conditions and allows searching for their interacting mRNA targets, GO annotation and their involvement in various biological pathways. The ARMOUR database includes a provision for adding more experimental data from users, with an aim to develop it as a platform for sharing and comparing experimental data contributed by research groups working on rice.

  8. Mobile Motion Capture--MiMiC.

    Science.gov (United States)

    Harbert, Simeon D; Jaiswal, Tushar; Harley, Linda R; Vaughn, Tyler W; Baranak, Andrew S

    2013-01-01

    The low cost, simple, robust, mobile, and easy to use Mobile Motion Capture (MiMiC) system is presented and the constraints which guided the design of MiMiC are discussed. The MiMiC Android application allows motion data to be captured from kinematic modules such as Shimmer 2r sensors over Bluetooth. MiMiC is cost effective and can be used for an entire day in a person's daily routine without being intrusive. MiMiC is a flexible motion capture system which can be used for many applications including fall detection, detection of fatigue in industry workers, and analysis of individuals' work patterns in various environments.

  9. An indigenous community mental health service on the Tohono O'odham (Papago) Indian Reservation: seventeen years later.

    Science.gov (United States)

    Kahn, M W; Lejero, L; Antone, M; Francisco, D; Manuel, J

    1988-06-01

    The status of a fully indigenous mental health program serviced and controlled by the Tohono O'odham (Papago) Indian tribe is reviewed from the perspective of its 17-year history. The program functions in large measure in a crisis intervention model, with suicidal or acutely disturbed cases being most frequent. However, a whole range of disorders and ages are seen. Traditional Medicine Men and Women are often used as consultants, as are some professionals. In recent years child sex abuse and abuse of drugs among youth are prominent problems. The program experienced problems of obtaining services off reservations for patients in need, and in establishing credibility of the Indian Mental Health workers with the outside service providers.

  10. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

    Science.gov (United States)

    Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

    2015-11-03

    Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

  11. Assessing Differences in the Availability of Opioid Addiction Therapy Options: Rural Versus Urban and American Indian Reservation Versus Non-Reservation

    Science.gov (United States)

    Hirchak, Katherine A.; Murphy, Sean M.

    2017-01-01

    Background Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use-disorder therapy. Purpose Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. Methods The unit of analysis was the zip code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18–64 in a zip code. A region was defined as a zip code and its contiguous zip codes. The independent variables were binary measures of whether a zip code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. Results The number of OAT clinics in a region per 10,000 zip-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 zip-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). Conclusions It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. PMID:26987797

  12. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Qiu Shuwei

    2013-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. Methods Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS and progression-free survival (PFS associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. Results In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP. More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model

  13. ARMOUR – A Rice miRNA: mRNA Interaction Resource

    Directory of Open Access Journals (Sweden)

    Neeti Sanan-Mishra

    2018-05-01

    Full Text Available ARMOUR was developed as ARice miRNA:mRNA interaction resource. This informative and interactive database includes the experimentally validated expression profiles of miRNAs under different developmental and abiotic stress conditions across seven Indian rice cultivars. This comprehensive database covers 689 known and 1664 predicted novel miRNAs and their expression profiles in more than 38 different tissues or conditions along with their predicted/known target transcripts. The understanding of miRNA:mRNA interactome in regulation of functional cellular machinery is supported by the sequence information of the mature and hairpin structures. ARMOUR provides flexibility to users in querying the database using multiple ways like known gene identifiers, gene ontology identifiers, KEGG identifiers and also allows on the fly fold change analysis and sequence search query with inbuilt BLAST algorithm. ARMOUR database provides a cohesive platform for novel and mature miRNAs and their expression in different experimental conditions and allows searching for their interacting mRNA targets, GO annotation and their involvement in various biological pathways. The ARMOUR database includes a provision for adding more experimental data from users, with an aim to develop it as a platform for sharing and comparing experimental data contributed by research groups working on rice.

  14. Bioinformatics of cardiovascular miRNA biology.

    Science.gov (United States)

    Kunz, Meik; Xiao, Ke; Liang, Chunguang; Viereck, Janika; Pachel, Christina; Frantz, Stefan; Thum, Thomas; Dandekar, Thomas

    2015-12-01

    MicroRNAs (miRNAs) are small ~22 nucleotide non-coding RNAs and are highly conserved among species. Moreover, miRNAs regulate gene expression of a large number of genes associated with important biological functions and signaling pathways. Recently, several miRNAs have been found to be associated with cardiovascular diseases. Thus, investigating the complex regulatory effect of miRNAs may lead to a better understanding of their functional role in the heart. To achieve this, bioinformatics approaches have to be coupled with validation and screening experiments to understand the complex interactions of miRNAs with the genome. This will boost the subsequent development of diagnostic markers and our understanding of the physiological and therapeutic role of miRNAs in cardiac remodeling. In this review, we focus on and explain different bioinformatics strategies and algorithms for the identification and analysis of miRNAs and their regulatory elements to better understand cardiac miRNA biology. Starting with the biogenesis of miRNAs, we present approaches such as LocARNA and miRBase for combining sequence and structure analysis including phylogenetic comparisons as well as detailed analysis of RNA folding patterns, functional target prediction, signaling pathway as well as functional analysis. We also show how far bioinformatics helps to tackle the unprecedented level of complexity and systemic effects by miRNA, underlining the strong therapeutic potential of miRNA and miRNA target structures in cardiovascular disease. In addition, we discuss drawbacks and limitations of bioinformatics algorithms and the necessity of experimental approaches for miRNA target identification. This article is part of a Special Issue entitled 'Non-coding RNAs'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer

    International Nuclear Information System (INIS)

    Schee, Kristina; Boye, Kjetil; Abrahamsen, Torveig Weum; Fodstad, Øystein; Flatmark, Kjersti

    2012-01-01

    MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and can function as oncogenes or tumor suppressors depending on the target. In this study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed. The miRNAs were chosen based on previous studies for their biomarker potential and suggested biological relevance in colorectal cancer. The miRNA expression was examined by qRT-PCR. Associations between miRNA expression and clinicopathological variables were explored using Mann–Whitney U and Kruskal-Wallis test while survival was estimated using the Kaplan-Meier method and compared using the log-rank test. MiR-101 was hardly expressed in the tumor samples, while for the other miRNAs, variable expression levels and expression ranges were observed, with miR-21 being most abundantly expressed relative to the reference (RNU44). In our study cohort, major clinical significance was demonstrated only for miR-31, as high expression was associated with advanced tumor stage and poor differentiation. No significant associations were found between expression of the investigated miRNAs and metastasis-free or overall survival. Investigating the expression of six miRNAs previously identified as candidate biomarkers in colorectal cancer, few clinically relevant associations were detected in our patient cohort. Our results emphasize the importance of validating potential tumor markers in independent patient cohorts, and indicate that the role of miRNAs as colorectal cancer biomarkers is still undetermined

  16. MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

    Science.gov (United States)

    Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua

    2016-11-01

    In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Genome-wide miRNA screening reveals miR-310 family members negatively regulate the immune response in Drosophila melanogaster via co-targeting Drosomycin.

    Science.gov (United States)

    Li, Yao; Li, Shengjie; Li, Ruimin; Xu, Jiao; Jin, Ping; Chen, Liming; Ma, Fei

    2017-03-01

    Although innate immunity mediated by Toll signaling has been extensively studied in Drosophila melanogaster, the role of miRNAs in regulating the Toll-mediated immune response remains largely unknown. In this study, following Gram-positive bacterial challenge, we identified 93 differentially expressed miRNAs via genome-wide miRNA screening. These miRNAs were regarded as immune response related (IRR). Eight miRNAs were confirmed to be involved in the Toll-mediated immune response upon Gram-positive bacterial infection through genetic screening of 41 UAS-miRNA lines covering 60 miRNAs of the 93 IRR miRNAs. Interestingly, four out of these eight miRNAs, miR-310, miR-311, miR-312 and miR-313, are clustered miRNAs and belong to the miR-310 family. These miR-310 family members were shown to target and regulate the expression of Drosomycin, an antimicrobial peptide produced by Toll signaling. Taken together, our study implies important regulatory roles of miRNAs in the Toll-mediated innate immune response of Drosophila upon Gram-positive bacterial infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Meaning in life experience at the end of life: validation of the Hindi version of the Schedule for Meaning in Life Evaluation and a cross-cultural comparison between Indian and German palliative care patients.

    Science.gov (United States)

    Kudla, Dorothea; Kujur, Julius; Tigga, Sumanti; Tirkey, Prakash; Rai, Punita; Fegg, Martin Johannes

    2015-01-01

    The experience of Meaning in Life (MiL) is a major protective factor against feelings of hopelessness and wishes for hastened death in palliative care (PC) patients. However, most instruments for MiL assessment have been developed only in Western countries so far. Little is known about MiL experience in Asian PC patients. This study aimed to provide a Hindi version of the Schedule for Meaning in Life Evaluation (SMiLE), test its feasibility and validity in Indian PC patients, and compare the results with previous studies in Germany. Indian PC patients in a hospice for the destitute were eligible to participate in this cross-sectional study. In the SMiLE instrument, respondents individually listed MiL-giving areas before rating their satisfaction with and importance of these areas. Overall indices of satisfaction (IoS, range 0-100), weighting (IoW, range 0-100), and weighted satisfaction (IoWS, range 0-100) were calculated. A Hindi forward-backward translation of the SMiLE was made. Two hundred fifty-eight Indian PC patients took part in the study (response rate 93.5%). Convergent validity of the SMiLE was found with the World Health Organization Quality of Life-Brief version (r = 0.17; P = 0.008) and the Idler Index of Religiosity (public religiousness: r = 0.25, P < 0.001 and private religiousness: r = 0.29, P < 0.001). Indian PC patients' IoW was 65.8 ± 22.1, IoS 68.6 ± 17.4, and IoWS 70.2 ± 17.0. In multivariate analyses of covariance, they differed significantly from German PC patients only in IoW (IoW: 84.8 ± 11.5, P < 0.001; IoS: 70.2 ± 19.7; IoWS: 72.0 ± 19.4). Compared with Germans, Indians more often listed spirituality (P < 0.001) and social commitment (P < 0.001) and less often social relations (P = 0.008). Preliminary results indicate good feasibility and validity of the Hindi version of the SMiLE. MiL experience also seems to be a coping resource for Indian PC patients. Copyright © 2015 American Academy of Hospice

  19. Simulation of the regional groundwater-flow system of the Menominee Indian Reservation, Wisconsin

    Science.gov (United States)

    Juckem, Paul F.; Dunning, Charles P.

    2015-01-01

    A regional, two-dimensional, steady-state groundwater-flow model was developed to simulate the groundwater-flow system and groundwater/surface-water interactions within the Menominee Indian Reservation. The model was developed by the U.S. Geological Survey (USGS), in cooperation with the Menominee Indian Tribe of Wisconsin, to contribute to the fundamental understanding of the region’s hydrogeology. The objectives of the regional model were to improve understanding of the groundwater-flow system, including groundwater/surface-water interactions, and to develop a tool suitable for evaluating the effects of potential regional water-management programs. The computer code GFLOW was used because of the ease with which the model can simulate groundwater/surface-water interactions, provide a framework for simulating regional groundwater-flow systems, and be refined in a stepwise fashion to incorporate new data and simulate groundwater-flow patterns at multiple scales. Simulations made with the regional model reproduce groundwater levels and stream base flows representative of recent conditions (1970–2013) and illustrate groundwater-flow patterns with maps of (1) the simulated water table and groundwater-flow directions, (2) probabilistic areas contributing recharge to high-capacity pumped wells, and (3) estimation of the extent of infiltrated wastewater from treatment lagoons.

  20. Facts about American Indian Education

    Science.gov (United States)

    American Indian College Fund, 2010

    2010-01-01

    As a result of living in remote rural areas, American Indians living on reservations have limited access to higher education. One-third of American Indians live on reservations, according to the U.S. Census Bureau. According to the most recent U.S. government statistics, the overall poverty rate for American Indians/Alaska Natives, including…

  1. Diabetes training for community health workers on an American Indian reservation.

    Science.gov (United States)

    Policicchio, Judith M; Dontje, Katherine

    2018-01-01

    To improve the knowledge and skills of community health workers (CHWs) on an American Indian (AI) Reservation related to the management of diabetes to allow CHWs, with no prior formal diabetes education to work more effectively with individuals in the community with diabetes. Training was provided in six "face-to-face" sessions with the CHWs using the Centers for Disease Control and Prevention CHW Training Resource on Heart Disease and Stroke. This is a quality improvement program guided by the Model for Improvement: Plan, Do, Study, Act and using a pre-post evaluation design. Ten AI CHWs were recruited for the training. Knowledge and attitudes, participation rates, and participant satisfaction were measured. Knowledge increased overall with largest changes in diabetes, depression and cholesterol. Diabetes attitudes were high and consistent with those found in caregivers who support patient-centered care. Participants reported learning, liking the class, and finding the materials helpful. This QI program provided by a public health nurse improved CHW's knowledge of diabetes and the management of diabetes. Next steps include formalizing the Reservation's CHW training program, expanding this training to other AI Health Service areas, and measuring the impact of CHWs in the community. © 2017 Wiley Periodicals, Inc.

  2. The miRNome of bipolar disorder.

    Science.gov (United States)

    Fries, Gabriel R; Carvalho, Andre F; Quevedo, Joao

    2018-06-01

    Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular significance according to recent studies. We aimed to summarize miRNA studies in BD to identify consistent findings, limitations, and future directions of this emerging field. We performed a comprehensive search on PUBMED and Medline for studies investigating an association between BD and miRNAs. The included studies report miRNA alterations in postmortem brain tissues and in the periphery, cell culture and preclinical findings, genetic associations, and the effects of medications. Several studies report changes in miRNA expression levels in postmortem brain and in the periphery of patients, although most of the results so far have not been replicated and are not concordant between different populations. Genetic studies also suggest that miRNA genes are located within susceptibility loci of BD, and also a putative role of miRNAs in modulating genes previously shown to confer risk of BD. We did not perform a systematic review of the literature, and miRNAs represent only one facet of the plethora of epigenetic mechanisms that might be involved in BD's pathophysiology. miRNA findings in BD significantly vary between studies, but are consistent to suggest a key role for these molecules in BD's pathophysiology and treatment, particularly miR-34a and miR-137. Accordingly, miRNA might represent important biomarkers of illness to be used in the clinical settings, and potentially also for the development of novel therapeutics for BD in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A values-based Motivational Interviewing (MI) intervention for pediatric obesity: study design and methods for MI Values.

    Science.gov (United States)

    Bean, Melanie K; Mazzeo, Suzanne E; Stern, Marilyn; Bowen, Deborah; Ingersoll, Karen

    2011-09-01

    To reduce pediatric obesity in clinical settings, multidisciplinary behaviorally-based treatment programs are recommended. High attrition and poor compliance are two difficulties frequently encountered in such programs. A brief, empathic and directive clinical intervention, Motivational Interviewing (MI), might help address these motivational and behavioral issues, ultimately resulting in more positive health outcomes. The efficacy of MI as an adjunct in the treatment of pediatric obesity remains relatively understudied. MI Values was developed to implement within an existing multidisciplinary treatment program for obese, ethnically diverse adolescents, the T.E.E.N.S. Program (Teaching, Encouragement, Exercise, Nutrition, Support). T.E.E.N.S. participants who consent to MI Values are randomized to either MI or an education control condition. At weeks 1 and 10 of T.E.E.N.S. participation, the subset of participants assigned to the MI condition engages in individual MI sessions and control participants view health education videos. All MI sessions are audiotaped and coded to monitor treatment fidelity, which has been satisfactory thus far. Participants complete comprehensive assessments at baseline, 3- and 6-month follow-ups. We hypothesize that MI participants will demonstrate greater reductions in Body Mass Index (BMI) percentile, improved diet and physical activity behaviors, better compliance with T.E.E.N.S., and lower attrition than participants in the control group. We present study design and methods for MI Values as well as data on feasibility of recruitment methods and treatment integrity. At study completion, findings will contribute to the emerging literature examining the efficacy of MI in the treatment of pediatric obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Water resources of the Prairie Island Indian Reservation, Minnesota, 1994-97

    Science.gov (United States)

    Cowdery, Timothy K.

    1999-01-01

    This evaluation of the water resources on the Prairie Island Indian Reservation includes data collected from 8 surface-water sites and 22 wells during 1994–97 and historical data. The Mississippi River and the lakes and wetlands connected to it are separated from the Vermillion River and the lakes and wetlands connected to it by the surficial aquifer on Prairie Island and by Lock and Dam Number 3. These surface-water groups form hydrologic boundaries of the surficial aquifer. The aquifer is 130–200 feet thick, extends to bedrock (the Franconia Formation, which is also an aquifer), and is composed primarily of sand and gravel, but also contains thin, isolated lenses of finer-grained material. Flow in the surficial aquifer is normally from the Mississippi River to the Vermillion River (southwest). During spring snowmelt or heavy rains, a ground-water mound forms in the center of the study area and causes radial ground-water flow toward the surrounding surface waters.

  5. miR-15a/miR-16 cluster inhibits invasion of prostate cancer cells by suppressing TGF-β signaling pathway.

    Science.gov (United States)

    Jin, Wei; Chen, Fangjie; Wang, Kefeng; Song, Yan; Fei, Xiang; Wu, Bin

    2018-05-23

    To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. 25 CFR 23.32 - Purpose of off-reservation grants.

    Science.gov (United States)

    2010-04-01

    ... Indian foster and adoptive children with the goal of strengthening and stabilizing Indian families; (c... Grants to Off-Reservation Indian Organizations for Title II Indian Child and Family Service Programs § 23... family service programs for the purpose of stabilizing Indian families and tribes, preventing the breakup...

  7. miR-184 and miR-150 promote renal glomerular mesangial cell aging by targeting Rab1a and Rab31.

    Science.gov (United States)

    Liu, Xiujuan; Fu, Bo; Chen, Dapeng; Hong, Quan; Cui, Jing; Li, Jin; Bai, Xueyuan; Chen, Xiangmei

    2015-08-15

    The molecular mechanism of kidney aging is not well understood, but the abnormal expression of miRNAs with aging is considered to be an important contributor. miR-184 and miR-150 were screened using a miRNA microarray and qRT-PCR and found to be significantly upregulated in 24-month-old rats. Rat renal primary glomerular mesangial cells (GMCs) were isolated from 3-month and 24-month-old rats for the in vitro analysis of the roles of miR-184 and miR-150 in kidney aging. Bioinformatics analyses suggested that Rab1a and Rab31, which are associated with cell autophagy, were targeted by both miR-184 and miR-150. miR-184 and miR-150 were increased significantly in aging GMCs versus young cells, while Rab1a and Rab31 were significantly lower in aging cells. Furthermore, dual luciferase reporter assays revealed that miR-184 and miR-150 bound to the 3'-UTR of Rab1a and Rab31 mRNAs. Transfection of miR-184 and miR-150 mimics into young GMCs suppressed the expression of Rab1a and Rab31. Transfected cells showed lower autophagy activities and higher levels of cellular oxidative products, leading to the aging of young GMCs. However, miR-184 and miR-150 inhibitors promoted autophagy and reduced oxidative damage by upregulating Rab1a and Rab31 in old GMCs. In conclusion, miR-184 and miR-150 inhibited autophagy, promoting GMC aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.

    Science.gov (United States)

    Fernández, Concepción; Bellosillo, Beatriz; Ferraro, Mariana; Seoane, Agustín; Sánchez-González, Blanca; Pairet, Silvia; Pons, Aina; Barranco, Luis; Vela, María Carmen; Gimeno, Eva; Colomo, Lluís; Besses, Carles; Navarro, Alfons; Salar, Antonio

    2017-01-02

    Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Federal and state permits required to open a new uranium mine with comments on uranium development on Indian reservations

    International Nuclear Information System (INIS)

    Root, T.E.; Whisler, J.S.

    1976-01-01

    Three federally related problems are discussed: the environmental impact statement, water discharge permits, and access. A cookbook approach to the permitting process is given as it exists in Wyoming, Utah, New Mexico, and Arizona. The question of jurisdiction is dealt with by using a case study approach to illustrate how jurisdiction bears on uranium development on Indian reservations

  10. Decreased neutrophil-associated miRNA and increased B-cell associated miRNA expression during tuberculosis.

    Science.gov (United States)

    van Rensburg, I C; du Toit, L; Walzl, G; du Plessis, N; Loxton, A G

    2018-05-20

    MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases. The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Reference miRNAs for miRNAome analysis of urothelial carcinomas.

    Directory of Open Access Journals (Sweden)

    Nadine Ratert

    Full Text Available BACKGROUND/OBJECTIVE: Reverse transcription quantitative real-time PCR (RT-qPCR is widely used in microRNA (miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma. METHODS: Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. PRINCIPAL FINDINGS: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. CONCLUSIONS: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p or three (miR-148b, miR-181b, and miR-874

  12. 77 FR 47868 - Indian Entities Recognized and Eligible To Receive Services From the Bureau of Indian Affairs

    Science.gov (United States)

    2012-08-10

    ... Indian Colony of California) Buena Vista Rancheria of Me-Wuk Indians of California Burns Paiute Tribe... of Idaho La Jolla Band of Luiseno Indians, California (previously listed as the La Jolla Band of Luiseno Mission Indians of the La Jolla Reservation) La Posta Band of Diegueno Mission Indians of the La...

  13. Intervention effects on kindergarten and first-grade teachers' classroom food practices and food-related beliefs in American Indian reservation schools.

    Science.gov (United States)

    Arcan, Chrisa; Hannan, Peter J; Himes, John H; Fulkerson, Jayne A; Rock, Bonnie Holy; Smyth, Mary; Story, Mary

    2013-08-01

    Prevalence of obesity among American Indian children is higher than the general US population. The school environment and teachers play important roles in helping students develop healthy eating habits. The aim of this prospective study was to examine teachers' classroom and school food practices and beliefs and the effect of teacher training on these practices and beliefs. Data were used from the Bright Start study, a group-randomized, school-based trial that took place on the Pine Ridge American Indian reservation (fall 2005 to spring 2008). Kindergarten and first-grade teachers (n=75) from 14 schools completed a survey at the beginning and end of the school year. Thirty-seven survey items were evaluated using mixed-model analysis of variance to examine the intervention effect for each teacher-practice and belief item (adjusting for teacher type and school as random effect). At baseline, some teachers reported classroom and school food practices and beliefs that supported health and some that did not. The intervention was significantly associated with lower classroom use of candy as a treat (P=0.0005) and fast-food rewards (P=0.008); more intervention teachers disagreed that fast food should be offered as school lunch alternatives (P=0.019), that it would be acceptable to sell unhealthy foods as part of school fundraising (P=0.006), and that it would not make sense to limit students' food choices in school (P=0.035). School-based interventions involving teacher training can result in positive changes in teachers' classroom food practices and beliefs about the influence of the school food environment in schools serving American Indian children on reservations. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  14. 25 CFR 39.721 - What transportation information must off-reservation boarding schools report?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What transportation information must off-reservation boarding schools report? 39.721 Section 39.721 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... transportation information must off-reservation boarding schools report? (a) Each off-reservation boarding school...

  15. Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry.

    Science.gov (United States)

    Singh, Avinainder; Collins, Bradley L; Gupta, Ankur; Fatima, Amber; Qamar, Arman; Biery, David; Baez, Julio; Cawley, Mary; Klein, Josh; Hainer, Jon; Plutzky, Jorge; Cannon, Christopher P; Nasir, Khurram; Di Carli, Marcelo F; Bhatt, Deepak L; Blankstein, Ron

    2018-01-23

    Despite significant progress in primary prevention, the rate of MI has not declined in young adults. The purpose of this study was to evaluate statin eligibility based on the 2013 American College of Cardiology/American Heart Association guidelines for treatment of blood cholesterol and 2016 U.S. Preventive Services Task Force recommendations for statin use in primary prevention in a cohort of adults who experienced a first-time myocardial infarction (MI) at a young age. The YOUNG-MI registry is a retrospective cohort from 2 large academic centers, which includes patients who experienced an MI at age ≤50 years. Diagnosis of type 1 MI was adjudicated by study physicians. Pooled cohort risk equations were used to estimate atherosclerotic cardiovascular disease risk score based on data available prior to MI or at the time of presentation. Of 1,685 patients meeting inclusion criteria, 210 (12.5%) were on statin therapy prior to MI and were excluded. Among the remaining 1,475 individuals, the median age was 45 years, there were 294 (20%) women, and 846 (57%) had ST-segment elevation MI. At least 1 cardiovascular risk factor was present in 1,225 (83%) patients. The median 10-year atherosclerotic cardiovascular disease risk score of the cohort was 4.8% (interquartile range: 2.8% to 8.0%). Only 724 (49%) and 430 (29%) would have met criteria for statin eligibility per the 2013 American College of Cardiology/American Heart Association guidelines and 2016 U.S. Preventive Services Task Force recommendations, respectively. This finding was even more pronounced in women, in whom 184 (63%) were not eligible for statins by either guideline, compared with 549 (46%) men (p adults who present with an MI at a young age would not have met current guideline-based treatment thresholds for statin therapy prior to their MI. These findings highlight the need for better risk assessment tools among young adults. Copyright © 2018 American College of Cardiology Foundation. Published by

  16. Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging.

    Science.gov (United States)

    Olivieri, Fabiola; Capri, Miriam; Bonafè, Massimiliano; Morsiani, Cristina; Jung, Hwa Jin; Spazzafumo, Liana; Viña, Jose; Suh, Yousin

    2017-07-01

    Human aging is a lifelong process characterized by a continuous trade-off between pro-and anti-inflammatory responses, where the best-adapted and/or remodeled genetic/epigenetic profile may develop a longevity phenotype. Centenarians and their offspring represent such a phenotype and their comparison to patients with age-related diseases (ARDs) is expected to maximize the chance to unravel the genetic makeup that better associates with healthy aging trajectories. Seemingly, such comparison is expected to allow the discovery of new biomarkers of longevity together with risk factor for the most common ARDs. MicroRNAs (miRNAs) and their shuttles (extracellular vesicles in particular) are currently conceived as those endowed with the strongest ability to provide information about the trajectories of healthy and unhealthy aging. We review the available data on miRNAs in aging and underpin the evidence suggesting that circulating miRNAs (and cognate shuttles), especially those involved in the regulation of inflammation (inflamma-miRs) may constitute biomarkers capable of reliably depicting healthy and unhealthy aging trajectories. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Relationship of Psychosocial Risk Factors, Certain Personality Traits and Myocardial Infarction in Indians: A Case-control Study.

    Science.gov (United States)

    Gupta, Rajni; Kishore, Jugal; Bansal, Yogesh; Daga, Mk; Jiloha, Rc; Singal, Rajeev; Ingle, Gk

    2011-07-01

    To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI). A case-control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi. Stress over 1 year was significantly higher in cases (P introvert (P < 0.001) personalities. Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients.

  18. miRConnect: Identifying Effector Genes of miRNAs and miRNA Families in Cancer Cells

    DEFF Research Database (Denmark)

    Hua, Youjia; Duan, Shiwei; Murmann, Andrea E

    2011-01-01

    have generated custom data sets containing expression information of 54 miRNA families sharing the same seed match. We have developed a novel strategy for correlating miRNAs with individual genes based on a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico titration experiment......micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of most mRNAs. They are powerful regulators of various differentiation stages, and the expression of genes that either negatively or positively correlate with expressed miRNAs is expected to hold information....... By focusing on the genes that correlate with the expression of miRNAs without necessarily being direct targets of miRNAs, we have clustered miRNAs into different functional groups. This has resulted in the identification of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition (EMT...

  19. Potential of breccia pipes in the Mohawk Canyon Area, Hualapai Indian Reservation, Arizona

    International Nuclear Information System (INIS)

    Wenrich, K.J.; Billingsley, G.H.; Van Gosen, B.S.

    1990-01-01

    The Hualapai Indian Reservation is on the southwestern corner of the Colorado Plateau in northern Arizona. Hundreds of solution-collapse breccia pipes crop out in the canyons and on the plateaus of northern Arizona. The pipes originated in the Mississippian Redwall Limestone and stoped their way upward through the upper Paleozoic strata, locally extending into the Triassic Moenkopi and Chinle Formations. The occurrence of high-grade U ore, associated with potentially economic concentrations of Cu, Ag, Pb, Zn, V, Co, and Ni in some of these pipes, has stimulated mining activity in northern Arizona despite the depressed market for most of these metals. Two breccia pipes, 241, and 242, have significant mineralized rock exposed on the Esplanade erosion surface; unfortunately, their economic potential is questionable because of their inaccessibility at the bottom of Mohawk Canyon. All warrant further exploration

  20. Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations.

    Directory of Open Access Journals (Sweden)

    Nalini Venkatesan

    Full Text Available To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort.Based on chromosomal 3 aberration, UM (n = 86 were grouped into monosomy 3 (M3; n = 51 and disomy 3 (D3; n = 35 by chromogenic in-situ hybridisation (CISH. The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE UM samples (n = 6 using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86 and mRNAs were validated in frozen UM (n = 10 by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52.Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0. Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134 were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated.UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

  1. Expression profiling of miR-96, miR-584 and miR-422a in colon ...

    African Journals Online (AJOL)

    Purpose: To determine the correlation between miRNAs; miR-96, miR-422a and miR584, and colon cancer, and also to test whether any of these miRNAs can act as non-invasive biomarkers in colon cancer. Methods: The tumor samples and the corresponding normal mucosa used in this study were collected from 60 ...

  2. Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients.

    Science.gov (United States)

    Barry, Simone E; Chan, Brian; Ellis, Magda; Yang, YuRong; Plit, Marshall L; Guan, Guangyu; Wang, Xiaolin; Britton, Warwick J; Saunders, Bernadette M

    2015-07-01

    Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Impact of miR-155 and miR-126 as novel biomarkers on the assessment of disease progression and prognosis in adult T-cell leukemia.

    Science.gov (United States)

    Ishihara, Kaori; Sasaki, Daisuke; Tsuruda, Kazuto; Inokuchi, Naoko; Nagai, Kazuhiro; Hasegawa, Hiroo; Yanagihara, Katsunori; Kamihira, Shimeru

    2012-12-01

    Micro RNAs (miRNAs) provide new insight in the development of cancer, but little is known about their clinical relevance as biomarkers in the assessment of diagnosis, classification, progression and prognosis of various cancers. To explore a potential novel biomarker, we examined the cellular and plasma miRNA profiles in adult T-cell leukemia (ATL) characterized by diverse clinical features. Using CD4-positive cells isolated from 2 non-infected healthy individuals, 3 chronic ATL patients and 3 acute ATL patients, cellular miRNAs were profiled by microarray. The microarray screened 5 miRNAs namely miR-155, let-7g, miR-126, miR-130a and let-7b because of the large difference in their expression in diseased vs. that of healthy controls. The expression levels of before 5 miRNAs re-quantified by reverse transcription quantifiable polymerase chain reaction (RT-qPCR) were not always accordant in cells and plasma. The high and low plasma levels of miR-155 and miR-126 changed with ATL stage. The present study revealed that there is a quantitative discrepancy between cellular and plasma miRNAs. The elevation of plasma miR-155 and the reduction in miR-126 correlated with poor prognosis, indicating their usefulness as a novel biomarker for the assessment of disease stage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Relationship of Psychosocial Risk Factors, Certain Personality Traits and Myocardial Infarction in Indians: A Case–control Study

    Science.gov (United States)

    Gupta, Rajni; Kishore, Jugal; Bansal, Yogesh; Daga, MK; Jiloha, RC; Singal, Rajeev; Ingle, GK

    2011-01-01

    Objective: To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI). Materials and Methods: A case–control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi. Results: Stress over 1 year was significantly higher in cases (P introvert (P < 0.001) personalities. Conclusion: Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients. PMID:22090670

  5. Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice.

    Science.gov (United States)

    Liu, Hui; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

    2015-12-01

    MicroRNAs are small noncoding RNAs that negatively regulate gene expression by binding to the untranslated regions of their target mRNAs. Deregulation of miRNAs is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of miR-34a and miR-483-3p by RNA sequencing (RNA-Seq) analyses. Real-time PCR further shows a 3- and 6-fold upregulation (respectively) of miR-34a in the AH livers and in the livers of DDC re-fed mice, while miR-483-3p was significantly downregulated in AH and DDC re-fed mice livers. This indicates that miR-34a and miR-483-3p may be crucial for liver MDB formation. P53 mRNA was found to be significantly downregulated both in the AH livers and in the livers of DDC re-fed mice, indicating that the upregulation of miR-34a is permitted by the decrease of p53 in AH since miR-34a is a main target of p53. Overexpression of miR-34a leads to an increase of p53 targets such as p27, which inhibits the cell cycle leading to cell cycle arrest. Importantly, BRCA1 is a target gene of miR-483-3p by RNA-Seq analyses and the downregulation of miR-483-3p may be the mechanism for liver MDB formation since the BRCA1 signal was markedly upregulated in AH livers. These results constitute a demonstration of the altered regulation of miR-34a and miR-483-3p in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by miR-34a and miR-483-3p in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Anatomy of an interrupted irrigation season: Micro-drought at the Wind River Indian Reservation

    Directory of Open Access Journals (Sweden)

    Shannon M. McNeeley

    Full Text Available Drought is a complex phenomenon manifested through interactions between biophysical and social factors. At the Wind River Indian Reservation (WRIR in west-central Wyoming, water shortages have become increasingly common since the turn of the 21st century. Here we discuss the 2015 water year as an exemplar year, which was characterized by wetter-than-normal conditions across the reservation and, according to the U.S. Drought Monitor, remained drought-free throughout the year. Yet parts of the reservation experienced harmful water shortages, or “micro-drought” conditions, during the growing season in 2015. In this assessment of the 2015 water year at the WRIR we: (1 describe the hydroclimatic and social processes under way that contributed to the 2015 water year micro-drought in the Little Wind Basin; (2 compare water availability conditions within and between other basins at the WRIR to illustrate how micro-droughts can result from social and environmental features unique to local systems; and (3 describe how a collaborative project is supporting drought preparedness at the WRIR. We combine a social science assessment with an analysis of the hydroclimate to deconstruct how shortages manifest at the WRIR. We provide insights from this study to help guide drought assessments at local scales. Keywords: Drought, Climate vulnerability, Drought preparedness, Indigenous adaptation, Co-production

  7. Measurement of target and double-spin asymmetries for the <mi>e><mi>peπ+(n>) reaction in the nucleon resonance region at low <mi>Q>2

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, X.; Adhikari, K. P.; Bosted, P.; Deur, A.; Drozdov, V.; El Fassi, L.; Kang, Hyekoo; Kovacs, K.; Kuhn, S.; Long, E.; Phillips, S. K.; Ripani, M.; Slifer, K.; Smith, L. C.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Asryan, G.; Avakian, H.; Badui, R. A.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Briscoe, W. J.; Bültmann, S.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chen, J. -P.; Chetry, T.; Choi, Seonho; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Compton, N.; Contalbrigo, M.; Crede, V.; D' Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Djalali, C.; Dodge, G. E.; Dupre, R.; Egiyan, H.; El Alaoui, A.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fersch, R.; Filippi, A.; Fleming, J. A.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Golovach, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Hanretty, C.; Harrison, N.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joosten, S.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, A.; Kim, W.; Klein, F. J.; Kubarovsky, V.; Lanza, L.; Lenisa, P.; Livingston, K.; MacGregor, I. J. D.; Markov, N.; McKinnon, B.; Mirazita, M.; Mokeev, V.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Peng, P.; Pisano, S.; Pogorelko, O.; Price, J. W.; Puckett, A. J. R.; Raue, B. A.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schumacher, R. A.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tian, Ye; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zhang, J.; Zonta, I.

    2016-10-01

    We report measurements of target- and double-spin asymmetries for the exclusive channel <mi>e><mi>peπ+(n>) in the nucleon resonance region at Jefferson Lab using the CEBAF Large Acceptance Spectrometer (CLAS). These asymmetries were extracted from data obtained using a longitudinally polarized NH3 target and a longitudinally polarized electron beam with energies 1.1, 1.3, 2.0, 2.3, and 3.0 GeV. The new results are consistent with previous CLAS publications but are extended to a low Q2 range from 0.0065 to 0.35 (GeV/c)2. The Q2 access was made possible by a custom-built Cherenkov detector that allowed the detection of electrons for scattering angles as low as 6 degrees. These results are compared with the unitary isobar models JANR and MAID, the partial-wave analysis prediction from SAID, and the dynamic model DMT. In many kinematic regions our results, in particular results on the target asymmetry, help to constrain the polarization-dependent components of these models.

  8. miRNA oligonucleotide and sponge for miRNA-21 inhibition mediated by PEI-PLL in breast cancer therapy.

    Science.gov (United States)

    Gao, Shiqian; Tian, Huayu; Guo, Ye; Li, Yuce; Guo, Zhaopei; Zhu, Xiaojuan; Chen, Xuesi

    2015-10-01

    anti-miR-21 oligonucleotide (AMO). PEI-PLL showed more transfection efficiency and lower cytotoxicity in human breast cancer cells than PEI. Moreover, the breast cancer cells exhibited significantly lower miR-21 expression and cell viability post transfection with sponge or AMO. Interestingly, the PEI-PLL/miR-21 inhibitor complexes also sensitized the cancer cells to anti-cancer chemotherapy drugs, doxorubicin (DOX) and cisplatin (CDDP). This synergistic effect provides a good application prospect of co-delivery miR-21 inhibitors and chemical drugs in breast cancer therapy. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.

    Science.gov (United States)

    Melnikova, Nataliya V; Dmitriev, Alexey A; Belenikin, Maxim S; Speranskaya, Anna S; Krinitsina, Anastasia A; Rachinskaia, Olga A; Lakunina, Valentina A; Krasnov, George S; Snezhkina, Anastasiya V; Sadritdinova, Asiya F; Uroshlev, Leonid A; Koroban, Nadezda V; Samatadze, Tatiana E; Amosova, Alexandra V; Zelenin, Alexander V; Muravenko, Olga V; Bolsheva, Nadezhda L; Kudryavtseva, Anna V

    2015-02-01

    Effective fertilizer application is necessary to increase crop yields and reduce risk of plant overdosing. It is known that expression level of microRNAs (miRNAs) alters in plants under different nutrient concentrations in soil. The aim of our study was to identify and characterize miRNAs with expression alterations under excessive fertilizer in agriculturally important crop - flax (Linum usitatissimum L.). We have sequenced small RNAs in flax grown under normal and excessive fertilizer using Illumina GAIIx. Over 14 million raw reads was obtained for two small RNA libraries. 84 conserved miRNAs from 20 families were identified. Differential expression was revealed for several flax miRNAs under excessive fertilizer according to high-throughput sequencing data. For 6 miRNA families (miR395, miR169, miR408, miR399, miR398 and miR168) expression level alterations were evaluated on the extended sampling using qPCR. Statistically significant up-regulation was revealed for miR395 under excessive fertilizer. It is known that target genes of miR395 are involved in sulfate uptake and assimilation. However, according to our data alterations of the expression level of miR395 could be associated not only with excess sulfur application, but also with redundancy of other macro- and micronutrients. Furthermore expression level was evaluated for miRNAs and their predicted targets. The negative correlation between miR399 expression and expression of its predicted target ubiquitin-conjugating enzyme E2 gene was shown in flax for the first time. So we suggested miR399 involvement in phosphate regulation in L. usitatissimum. Revealed in our study expression alterations contribute to miRNA role in flax response to excessive fertilizer. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  10. Involvement of miR160/miR393 and their targets in cassava responses to anthracnose disease.

    Science.gov (United States)

    Pinweha, Nattaya; Asvarak, Thipa; Viboonjun, Unchera; Narangajavana, Jarunya

    2015-02-01

    Cassava is a starchy root crop for food and industrial applications in many countries around the world. Among the factors that affect cassava production, diseases remain the major cause of yield loss. Cassava anthracnose disease is caused by the fungus Colletotrichum gloeosporioides. Severe anthracnose attacks can cause tip die-backs and stem cankers, which can affect the availability of planting materials especially in large-scale production systems. Recent studies indicate that plants over- or under-express certain microRNAs (miRNAs) to cope with various stresses. Understanding how a disease-resistant plant protects itself from pathogens should help to uncover the role of miRNAs in the plant immune system. In this study, the disease severity assay revealed different response to C. gloeosporioides infection in two cassava cultivars. Quantitative RT-PCR analysis uncovered the differential expression of the two miRNAs and their target genes in the two cassava cultivars that were subjected to fungal infection. The more resistant cultivar revealed the up-regulation of miR160 and miR393, and consequently led to low transcript levels in their targets, ARF10 and TIR1, respectively. The more susceptible cultivar exhibited the opposite pattern. The cis-regulatory elements relevant to defense and stress responsiveness, fungal elicitor responsiveness and hormonal responses were the most prevalent present in the miRNAs gene promoter regions. The possible dual role of these specific miRNAs and their target genes associated with cassava responses to C. gloeosporioides is discussed. This is the first study to address the molecular events by which miRNAs which might play a role in fungal-infected cassava. A better understanding of the functions of miRNAs target genes should greatly increase our knowledge of the mechanism underlying susceptibility and lead to new strategies to enhance disease tolerance in this economically important crop. Copyright © 2014 Elsevier GmbH. All

  11. Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuberculosis and associate with responses to therapy.

    Science.gov (United States)

    Wagh, Vishal; Urhekar, Anant; Modi, Deepak

    2017-01-01

    Identification of blood biomarkers that can be useful for predicting Mycobacterium tuberculosis (M.TB) infection, effect of therapy and Multi Drug Resistant (MDR) TB infected individuals is clinically useful for combating tuberculosis epidemic. In this study, we have evaluated the levels of selected miRNAs in serum of TB and MDR TB patients. In addition, we have studied their levels in serum of patients post-therapy. The levels of 4-miRNAs (miR-16, miR-29a, miR-125b and miR-155) were measured in 30 newly diagnosed TB patients, 19 Multi Drug Resistant (MDR) TB patients, 10 patients who completed TB therapy and were TB negative. 30 healthy individuals were recruited as controls. The levels of the miRNAs were estimated by qRT-PCR. Of the four miRNAs studied, the levels of miR-16 were significantly elevated and miR-155 were significantly reduced in serum of TB patients as compared to uninfected controls. The Receiver Operating Characteristic (ROC) curve of miR-16 and miR-155 exhibited a significant distinguishing efficiency with an AUC value of 1 (95% CI, 1 to 1) and 0.967 (95% CI, 0.92-1.04) respectively. Following the therapy, the levels of miR-16 and miR-155 returned to those observed in healthy subjects. In patients with MDR TB, miR-155 was lower as compared to healthy controls and TB treated group but higher as compared to TB naïve patients. miR-16 levels were lowest in serum of MDR TB patients compared to TB naïve, TB treated group and healthy controls. In conclusion, miR-16 and miR-155 in serum may act as surrogate biomarker for studying TB infection, progression of therapy and MDR TB. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Exploring miRNA based approaches in cancer diagnostics and therapeutics.

    Science.gov (United States)

    Mishra, Shivangi; Yadav, Tanuja; Rani, Vibha

    2016-02-01

    MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. 75 FR 5107 - Notice of Inventory Completion: U.S. Department of the Interior, Bureau of Indian Affairs...

    Science.gov (United States)

    2010-02-01

    ... Indian Reservation, San Xavier Indian Reservation, and Tohono O'odham Indian Reservation in Maricopa..., near Chuichui and the northern border of the Tohono O'odham Indian Reservation, Pinal County, AZ... River Pima-Maricopa Indian Community of the Salt River Reservation, Arizona; Tohono O'odham Nation of...

  14. miRSeqNovel

    DEFF Research Database (Denmark)

    Qian, Kui; Auvinen, Eeva; Greco, Dario

    2012-01-01

    We present miRSeqNovel, an R based workflow for miRNA sequencing data analysis. miRSeqNovel can process both colorspace (SOLiD) and basespace (Illumina/Solexa) data by different mapping algorithms. It finds differentially expressed miRNAs and gives conservative prediction of novel miRNA candidates...... with customized parameters. miRSeqNovel is freely available at http://sourceforge.net/projects/mirseq/files....

  15. 75 FR 58427 - Notice of Inventory Completion: Office of the State Archaeologist, Lansing, MI

    Science.gov (United States)

    2010-09-24

    ... Tribe of Indians of Oklahoma; Bad River Band of the Lake Superior Tribe of Chippewa Indians of the Bad... Absentee-Shawnee Tribe of Indians of Oklahoma; Bad River Band of the Lake Superior Tribe of Chippewa Indians of the Bad River Reservation, Wisconsin; Bay Mills Indian Community, Michigan; Bois Forte Band...

  16. Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression

    Czech Academy of Sciences Publication Activity Database

    Aherne, S.T.; Madden, S.F.; Hughes, D. J.; Pardini, B.; Naccarati, A.; Levý, M.; Vodička, Pavel; Neary, P.; Dowling, P.; Clynes, M.

    2015-01-01

    Roč. 15, apr 30 (2015), s. 2-13 ISSN 1471-2407 R&D Projects: GA ČR GAP304/10/1286 Institutional support: RVO:68378041 Keywords : colorectal cancer * circulating miRNAs * miR-34a * miR-150 * miR-923 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.265, year: 2015

  17. American Indian Community Colleges.

    Science.gov (United States)

    One Feather, Gerald

    With the emergence of reservation based community colleges (th Navajo Community College and the Dakota Community Colleges), the American Indian people, as decision makers in these institutions, are providing Indians with the technical skills and cultural knowledge necessary for self-determination. Confronted with limited numbers of accredited…

  18. Field screening of water quality, bottom sediment, and biota associated with irrigation drainage in and near Walker River Indian Reservation, Nevada 1994-95

    Science.gov (United States)

    Thodal, Carl E.; Tuttle, Peter L.

    1996-01-01

    A study was begun in 1994 to determine whether the quality of irrigation drainage from the Walker River Indian Reservation, Nevada, has caused or has potential to cause harmful effects on human health or on fish and wildlife, or may adversely affect the suitability of the Walker River for other beneficial uses. Samples of water, bottom sediment, and biota were collected during June-August 1994 (during a drought year) from sites upstream from and on the Walker River Indian Reservation for analyses of trace elements. Other analyses included physical characteristics, major dissolved constituents, selected species of water-soluble nitrogen and phosphorus, and selected pesticides in bottom sediment. Water samples were collected again from four sites on the Reservation in August 1995 (during a wetterthan- average year) to provide data for comparing extreme climatic conditions. Water samples collected from the Walker River Indian Reservation in 1994 equaled or exceeded the Nevada water-quality standard or level of concern for at least one of the following: water temperature, pH, dissolved solids, unionized ammonia, phosphate, arsenic, boron, chromium, lead, and molybdenum; in 1995, only a single sample from one site exceeded a Nevada water-quality standard for molybdenum. Levels of concern for trace elements in bottom sediment collected in 1994 were equaled or exceeded for arsenic, iron, manganese, and zinc. Concentrations of organochiorine pesticide residues in bottom sediment were below analytical reporting limits. Levels of concern for trace-elements in samples of biota were equaled or exceeded for arsenic, boron, copper, and mercury. Results of toxicity testing indicate that only water samples from Walker Lake caused a toxic response in test bacteria. Arsenic and boron concentrations in water, bottom sediment, and biological tissue exceeded levels of concern throughout the Walker River Basin, but most commonly in the lower Walker River Basin. Mercury also was elevated

  19. miREE: miRNA recognition elements ensemble

    Science.gov (United States)

    2011-01-01

    Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between

  20. About miRNAs, miRNA seeds, target genes and target pathways.

    Science.gov (United States)

    Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

    2017-12-05

    miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

  1. miRiadne: a web tool for consistent integration of miRNA nomenclature.

    Science.gov (United States)

    Bonnal, Raoul J P; Rossi, Riccardo L; Carpi, Donatella; Ranzani, Valeria; Abrignani, Sergio; Pagani, Massimiliano

    2015-07-01

    The miRBase is the official miRNA repository which keeps the annotation updated on newly discovered miRNAs: it is also used as a reference for the design of miRNA profiling platforms. Nomenclature ambiguities generated by loosely updated platforms and design errors lead to incompatibilities among platforms, even from the same vendor. Published miRNA lists are thus generated with different profiling platforms that refer to diverse and not updated annotations. This greatly compromises searches, comparisons and analyses that rely on miRNA names only without taking into account the mature sequences, which is particularly critic when such analyses are carried over automatically. In this paper we introduce miRiadne, a web tool to harmonize miRNA nomenclature, which takes into account the original miRBase versions from 10 up to 21, and annotations of 40 common profiling platforms from nine brands that we manually curated. miRiadne uses the miRNA mature sequence to link miRBase versions and/or platforms to prevent nomenclature ambiguities. miRiadne was designed to simplify and support biologists and bioinformaticians in re-annotating their own miRNA lists and/or data sets. As Ariadne helped Theseus in escaping the mythological maze, miRiadne will help the miRNA researcher in escaping the nomenclature maze. miRiadne is freely accessible from the URL http://www.miriadne.org. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Differential expression of miRNAs by macrophages infected with virulent and avirulent Mycobacterium tuberculosis.

    Science.gov (United States)

    Das, Kishore; Saikolappan, Sankaralingam; Dhandayuthapani, Subramanian

    2013-12-01

    MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate a wide range of biological processes that include cellular differentiation, development, immunity and apoptosis. There is a growing body of evidences that bacteria modulate immune responses by altering the expression of host miRNAs. Since macrophages are immune cells associated with innate and adaptive immunity, we investigated whether Mycobacterium tuberculosis infection affects miRNAs of macrophages. THP-1 macrophages infected with virulent (H37Rv) and avirulent (H37Ra) strains of M. tuberculosis were analyzed for changes in miRNAs' expression using microarray. This revealed that nine miRNA genes (miR-30a, miR-30e, miR-155, miR-1275, miR-3665, miR-3178, miR-4484, miR-4668-5p and miR-4497) were differentially expressed between THP-1cells infected with M. tuberculosis H37Rv and M. tuberculosis H37Ra strains. Additional characterization of these genes is likely to provide insights into their role in the pathogenesis of tuberculosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. miRNA regulation of LDL-cholesterol metabolism.

    Science.gov (United States)

    Goedeke, Leigh; Wagschal, Alexandre; Fernández-Hernando, Carlos; Näär, Anders M

    2016-12-01

    In the past decade, microRNAs (miRNAs) have emerged as key regulators of circulating levels of lipoproteins. Specifically, recent work has uncovered the role of miRNAs in controlling the levels of atherogenic low-density lipoprotein LDL (LDL)-cholesterol by post-transcriptionally regulating genes involved in very low-density lipoprotein (VLDL) secretion, cholesterol biosynthesis, and hepatic LDL receptor (LDLR) expression. Interestingly, several of these miRNAs are located in genomic loci associated with abnormal levels of circulating lipids in humans. These findings reinforce the interest of targeting this subset of non-coding RNAs as potential therapeutic avenues for regulating plasma cholesterol and triglyceride (TAG) levels. In this review, we will discuss how these new miRNAs represent potential pre-disposition factors for cardiovascular disease (CVD), and putative therapeutic targets in patients with cardiometabolic disorders. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Pharmaco-miR

    DEFF Research Database (Denmark)

    Rukov, Jakob Lewin; Wilentzik, Roni; Jaffe, Ishai

    2014-01-01

    MicroRNAs (miRNAs) are short regulatory RNAs that down-regulate gene expression. They are essential for cell homeostasis and active in many disease states. A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics......' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function. These interactions can be described as triplet sets consisting of a miRNA, a target gene and a drug associated with the gene. We have developed a web server which...... links miRNA expression and drug function by combining data on miRNA targeting and protein-drug interactions. miRNA targeting information derive from both experimental data and computational predictions, and protein-drug interactions are annotated by the Pharmacogenomics Knowledge base (Pharm...

  5. Comprehensive analysis of miRNAs expression profiles revealed potential key miRNA/mRNAs regulating colorectal cancer stem cell self-renewal.

    Science.gov (United States)

    Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

    2018-05-20

    Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells. Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer. Further, we constructed a miRNA-mRNA network, based on which, several miRNA/mRNA pairs were ranked according to their impact index to the self-renewal of colorectal cancer stem cells. Further biological experiment showed that up-regulation of miR-92a-3p led to cell cycle arrest and reduced colony formation. This work provides clues to find the new potential biomarkers for colorectal cancer stem cell diagnosis and select effective miRNAs for targeted therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    Science.gov (United States)

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  7. Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells.

    Science.gov (United States)

    Wang, Xinyu; Ren, Yanli; Wang, Zhiqiong; Xiong, Xiangyu; Han, Sichong; Pan, Wenting; Chen, Hongwei; Zhou, Liqing; Zhou, Changchun; Yuan, Qipeng; Yang, Ming

    2015-12-21

    5S rRNA plays an important part in ribosome biology and is over-expression in multiple cancers. In this study, we found that 5S rRNA is a direct target of miR-150 and miR-383 in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-150 and miR-383 inhibited ESCC cell proliferation in vitro and in vivo. Moreover, 5S rRNA silencing by miR-150 and miR-383 might intensify rpL11-c-Myc interaction, which attenuated role of c-Myc as an oncogenic transcriptional factor and dysregulation of multiple c-Myc target genes. Taken together, our results highlight the involvement of miRNAs in ribosomal regulation during tumorigenesis. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Food Environments around American Indian Reservations: A Mixed Methods Study.

    Science.gov (United States)

    Chodur, Gwen M; Shen, Ye; Kodish, Stephen; Oddo, Vanessa M; Antiporta, Daniel A; Jock, Brittany; Jones-Smith, Jessica C

    2016-01-01

    To describe the food environments experienced by American Indians living on tribal lands in California. Geocoded statewide food business data were used to define and categorize existing food vendors into healthy, unhealthy, and intermediate composite categories. Distance to and density of each of the composite food vendor categories for tribal lands and nontribal lands were compared using multivariate linear regression. Quantitative results were concurrently triangulated with qualitative data from in-depth interviews with tribal members (n = 24). After adjusting for census tract-level urbanicity and per capita income, results indicate there were significantly fewer healthy food outlets per square mile for tribal areas compared to non-tribal areas. Density of unhealthy outlets was not significantly different for tribal versus non-tribal areas. Tribal members perceived their food environment negatively and reported barriers to the acquisition of healthy food. Urbanicity and per capita income do not completely account for disparities in food environments among American Indians tribal lands compared to nontribal lands. This disparity in access to healthy food may present a barrier to acting on the intention to consume healthy food.

  9. Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer.

    Science.gov (United States)

    Lu, Ya-Ching; Chang, Joseph Tung-Chieh; Huang, Yu-Chen; Huang, Chi-Che; Chen, Wen-Ho; Lee, Li-Yu; Huang, Bing-Shen; Chen, Yin-Ju; Li, Hsiao-Fang; Cheng, Ann-Joy

    2015-02-01

    The aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer. To determine the stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients. In general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P oral cancer patients (9.3- and 17.0-fold, respectively; P cancer patients (AUC = 0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC = 0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC = 0.845) or oral cancer (AUC = 0.963), as well as in the prediction of potential malignancy (AUC = 0.950, sensitivity = 91%, specificity = 85%). Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. The Indian Gaming Regulatory Act and Its Effects on American Indian Economic Development

    OpenAIRE

    Randall K. Q. Akee; Katherine A. Spilde; Jonathan B. Taylor

    2015-01-01

    The Indian Gaming Regulatory Act (IGRA), passed by the US Congress in 1988, was a watershed in the history of policymaking directed toward reservation-resident American Indians. IGRA set the stage for tribal government-owned gaming facilities. It also shaped how this new industry would develop and how tribal governments would invest gaming revenues. Since then, Indian gaming has approached commercial, state-licensed gaming in total revenues. Gaming operations have had a far-reaching and trans...

  11. 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer

    African Journals Online (AJOL)

    RNAs (21 - 24 nucleotides in length) that are critical for many important processes such as development, ... RNA extraction and reverse transcription. Total RNA was extracted from each of the experimental groups using ... used as an endogenous control to normalize the expression of miRNA-143, miRNA-34A, miRNA-.

  12. Expression profiling of miR-96, miR-584 and miR-422a in colon ...

    African Journals Online (AJOL)

    . Lower miRNA ... Thus, the ratio of miR-96/miR-638 in plasma is a potential non- ... leading cause of cancer related deaths. ... breast cancer cells have revealed a total of 51 ... Corresponding negative control ..... The American Joint Committee.

  13. Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with AAA and Their Relationship to Clinical Outcomes after Endovascular Repair.

    Science.gov (United States)

    Tenorio, Emanuel Junio Ramos; Braga, Andre Felipe Farias; Tirapelli, Daniela Pretti Da Cunha; Ribeiro, Mauricio Serra; Piccinato, Carlos Eli; Joviliano, Edwaldo Edner

    2018-03-05

    The purpose of this study was to quantify and evaluate the expression response of miRNA-191 and miRNA-455-3p endovascular repair of abdominal aortic aneurysm (AAA) based in whole blood samples. This report describes a prospective study of a single center of 30 patients with AAA who underwent endovascular repair. Blood samples were collected preoperatively and 6 months postoperatively. The differential expression of the miRNAs was performed by the real-time polymerase chain reaction method, after extraction of the RNA from the blood samples at the 2 moments. In addition, bioinformatic tools were used to determine pathophysiological pathways related to AAA. The miR-191 and miR-455-3p were overexpressed preoperatively. After 6 months postoperatively, miR-191 (median 0.98, IQR 0.5-2.1, P AAA showed no significant differences in the expression of miR-191 and miR-455-3p. Exclusion of the aneurysmal sac after endovascular treatment induces a decrease in the expression of the studied miRNAs in whole blood samples, which suggests a possible use of them as biomarkers of therapeutic success. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. miR-193b Regulates Mcl-1 in Melanoma.

    Science.gov (United States)

    Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C; Yang, Xiaolong; Feilotter, Harriet E; Tron, Victor A

    2011-11-01

    MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. High-throughput characterization of Echinococcus spp. metacestode miRNomes.

    Science.gov (United States)

    Cucher, Marcela; Macchiaroli, Natalia; Kamenetzky, Laura; Maldonado, Lucas; Brehm, Klaus; Rosenzvit, Mara Cecilia

    2015-03-01

    Echinococcosis is a worldwide zoonosis of great public health concern, considered a neglected disease by the World Health Organisation. The cestode parasites Echinococcus granulosus sensu lato (s. l.) and Echinococcus multilocularis are the main aetiological agents. In the intermediate host, these parasites display particular developmental traits that lead to different patterns of disease progression. In an attempt to understand the causes of these differences, we focused on the analysis of microRNAs (miRNAs), small non-coding regulatory RNAs with major roles in development of animals and plants. In this work, we analysed the small RNA expression pattern of the metacestode, the stage of sanitary relevance, and provide a detailed description of Echinococcus miRNAs. Using high-throughput small RNA sequencing, we believe that we have carried out the first experimental identification of miRNAs in E. multilocularis and have expanded the Echinococcus miRNA catalogue to 38 miRNA genes, including one miRNA only present in E. granulosus s. l. Our findings show that although both species share the top five highest expressed miRNAs, 13 are differentially expressed, which could be related to developmental differences. We also provide evidence that uridylation is the main miRNA processing mechanism in Echinococcus spp. These results provide detailed information on Echinococcus miRNAs, which is the first step in understanding their role in parasite biology and disease establishment and/or progression, and their future potential use as drug or diagnostic targets. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  16. Ground-survey and water-quality data for selected wetlands on or near the Lower Brule Indian Reservation in South Dakota, 2012-13

    Science.gov (United States)

    Neitzert, Kathleen M.; Thompson, Ryan F.

    2015-08-20

    Numerous lakes, ponds, and wetlands are located within the Lower Brule Indian Reservation. Wetlands are an important resource providing aquatic habitat for plants and animals, and acting as a natural water filtration system. Several of the wetlands on or near the reservation are of particular interest, but information on the physical and biological integrity of these wetlands was needed to provide a base-line reference when planning for future water management needs. A reconnaissance-level study of selected wetlands on and near the Lower Brule Indian Reservation was completed in 2012–13 by the U.S. Geological Survey in cooperation with the Lower Brule Sioux Tribe using ground surveys and water-quality analyses. Ground surveys of six wetland areas (Dorman Slough, Little Bend Wetlands, Miller Pond, Potter Slough, an unnamed slough, and West Brule Community wetlands) were completed to map land, water, vegetation, and man-made features of the selected wetland areas using real-time kinematic global navigation satellite systems equipment. Water samples were collected from four of the selected wetlands. Two separate waterbodies were sampled at one of the wetlands for a total of five sampling locations. Water samples were analyzed for physical properties, selected inorganics, metals, nutrients, and suspended sediment. Concentrations of calcium, sodium, and sulfate were greater at the two wetland sites fed by ground water, compared to the wetland sites fed by surface runoff.

  17. Differential expression of miRNAs and their relation to active tuberculosis.

    Science.gov (United States)

    Xu, Zhihong; Zhou, Aiping; Ni, Jinjing; Zhang, Qiufen; Wang, Ying; Lu, Jie; Wu, Wenjuan; Karakousis, Petros C; Lu, Shuihua; Yao, Yufeng

    2015-07-01

    The aim of this work was to screen miRNA signatures dysregulated in tuberculosis to improve our understanding of the biological role of miRNAs involved in the disease. Datasets deposited in publically available databases from microarray studies on infectious diseases and malignancies were retrieved, screened, and subjected to further analysis. Effect sizes were combined using the inverse-variance model and between-study heterogeneity was evaluated by the random effects model. 35 miRNAs were differentially expressed (12 up-regulated, 23 down-regulated; p tuberculosis and other infectious diseases. 15 miRNAs were found to be significantly differentially regulated (7 up-regulated, 8 down-regulated; p tuberculosis and malignancies. Most of the miRNA signatures identified in this study were found to be involved in immune responses and metabolism. Expression of these miRNA signatures in serum samples from TB subjects (n = 11) as well as healthy controls (n = 10) was examined by TaqMan miRNA array. Taken together, the results revealed differential expression of miRNAs in TB, but available datasets are limited and these miRNA signatures should be validated in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. BIA Indian Lands Dataset (Indian Lands of the United States)

    Data.gov (United States)

    Federal Geographic Data Committee — The American Indian Reservations / Federally Recognized Tribal Entities dataset depicts feature location, selected demographics and other associated data for the 561...

  19. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  20. miR319, miR390, and miR393 Are Involved in Aluminum Response in Flax (Linum usitatissimum L.).

    Science.gov (United States)

    Dmitriev, Alexey A; Kudryavtseva, Anna V; Bolsheva, Nadezhda L; Zyablitsin, Alexander V; Rozhmina, Tatiana A; Kishlyan, Natalya V; Krasnov, George S; Speranskaya, Anna S; Krinitsina, Anastasia A; Sadritdinova, Asiya F; Snezhkina, Anastasiya V; Fedorova, Maria S; Yurkevich, Olga Yu; Muravenko, Olga V; Belenikin, Maxim S; Melnikova, Nataliya V

    2017-01-01

    Acid soils limit agricultural production worldwide. Major reason of crop losses in acid soils is the toxicity of aluminum (Al). In the present work, we investigated expression alterations of microRNAs in flax ( Linum usitatissimum L.) plants under Al stress. Flax seedlings of resistant (TMP1919 and G1071/4_k) and sensitive (Lira and G1071/4_o) to Al cultivars and lines were exposed to AlCl 3 solution for 4 and 24 hours. Twelve small RNA libraries were constructed and sequenced using Illumina platform. In total, 97 microRNAs from 18 conserved families were identified. miR319, miR390, and miR393 revealed expression alterations associated with Al treatment of flax plants. Moreover, for miR390 and miR393, the alterations were distinct in sensitive and resistant to Al genotypes. Expression level changes of miR319 and miR390 were confirmed using qPCR analysis. In flax, potential targets of miR319 are TCPs, miR390-TAS3 and GRF5, and miR393-AFB2-coding transcripts. TCPs, TAS3, GRF5, and AFB2 participate in regulation of plant growth and development. The involvement of miR319, miR390, and miR393 in response to Al stress in flax was shown here for the first time. We speculate that these microRNAs play an important role in Al response via regulation of growth processes in flax plants.

  1. Decreased Expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T Cells and Peripheral Blood from Tuberculosis Patients

    Science.gov (United States)

    Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M.; Jacobsen, Marc

    2013-01-01

    The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4+ T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease. PMID:23613882

  2. Food Environments around American Indian Reservations: A Mixed Methods Study.

    Directory of Open Access Journals (Sweden)

    Gwen M Chodur

    Full Text Available To describe the food environments experienced by American Indians living on tribal lands in California.Geocoded statewide food business data were used to define and categorize existing food vendors into healthy, unhealthy, and intermediate composite categories. Distance to and density of each of the composite food vendor categories for tribal lands and nontribal lands were compared using multivariate linear regression. Quantitative results were concurrently triangulated with qualitative data from in-depth interviews with tribal members (n = 24.After adjusting for census tract-level urbanicity and per capita income, results indicate there were significantly fewer healthy food outlets per square mile for tribal areas compared to non-tribal areas. Density of unhealthy outlets was not significantly different for tribal versus non-tribal areas. Tribal members perceived their food environment negatively and reported barriers to the acquisition of healthy food.Urbanicity and per capita income do not completely account for disparities in food environments among American Indians tribal lands compared to nontribal lands. This disparity in access to healthy food may present a barrier to acting on the intention to consume healthy food.

  3. There Shall We Be Also: Tribal Fractures and Auxiliaries in the Indian Wars of the Northern Great Plains

    Science.gov (United States)

    2008-11-20

    Director ~ Thomas A. BrUS ~h.D. Monograph Reader MiCh~~--- Director, School of Advanced Military Studies ~~~M ___ ’" Director, Robert F. Bau , Ph.D...Indians, Infants, and Infantry: Andrew and Elizabeth Burt on the Frontier (Lincoln, NE: University of Nebraska Press, 1988), 130-132; Dunlay, Wolves for...Indians, Infants, and Infantry: Andrew and Elizabeth Burt on the Frontier. Lincoln, NE: University of Nebraska Press, 1988. Morgan, Patrick. "How

  4. A compilation of Web-based research tools for miRNA analysis.

    Science.gov (United States)

    Shukla, Vaibhav; Varghese, Vinay Koshy; Kabekkodu, Shama Prasada; Mallya, Sandeep; Satyamoorthy, Kapaettu

    2017-09-01

    Since the discovery of microRNAs (miRNAs), a class of noncoding RNAs that regulate the gene expression posttranscriptionally in sequence-specific manner, there has been a release of number of tools useful for both basic and advanced applications. This is because of the significance of miRNAs in many pathophysiological conditions including cancer. Numerous bioinformatics tools that have been developed for miRNA analysis have their utility for detection, expression, function, target prediction and many other related features. This review provides a comprehensive assessment of web-based tools for the miRNA analysis that does not require prior knowledge of any computing languages. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. miR-192, miR-194 and miR-215: a convergent microRNA network suppressing tumor progression in renal cell carcinoma.

    Science.gov (United States)

    Khella, H W Z; Bakhet, M; Allo, G; Jewett, M A S; Girgis, A H; Latif, A; Girgis, H; Von Both, I; Bjarnason, G A; Yousef, G M

    2013-10-01

    MicroRNAs (miRNAs) play a crucial role in tumor progression and metastasis. We, and others, recently identified a number of miRNAs that are dysregulated in metastatic renal cell carcinoma compared with primary renal cell carcinoma. Here, we investigated three miRNAs that are significantly downregulated in metastatic tumors: miR-192, miR-194 and miR-215. Gain-of-function analyses showed that restoration of their expression decreases cell migration and invasion in renal cell carcinoma cell line models, whereas knockdown of these miRNAs resulted in enhancing cellular migration and invasion abilities. We identified three targets of these miRNAs with potential role in tumor aggressiveness: murine double minute 2, thymidylate synthase, and Smad Interacting protein 1/zinc finger E-box binding homeobox 2. We observed a convergent effect (the same molecule can be targeted by all three miRNAs) and a divergent effect (the same miRNA can control multiple targets) for these miRNAs. We experimentally validated these miRNA-target interactions using three independent approaches. First, we observed that miRNA overexpression significantly reduces the mRNA and protein levels of their targets. In the second, we observed significant reduction of the luciferase signal of a vector containing the 3'UTR of the target upon miRNA overexpression. Finally, we show the presence of inverse correlation between miRNA changes and the expression levels of their targets in patient specimens. We also examined the prognostic significance of miR-215 in renal cell carcinoma. Lower expression of miR-215 is associated with significantly reduced disease-free survival time. These findings were validated on an independent data set from The Cancer Genome Atlas. These results can pave the way to the clinical use of miRNAs as prognostic markers and therapeutic targets.

  6. 23 CFR 973.210 - Indian lands bridge management system (BMS).

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Indian lands bridge management system (BMS). 973.210... HIGHWAYS MANAGEMENT SYSTEMS PERTAINING TO THE BUREAU OF INDIAN AFFAIRS AND THE INDIAN RESERVATION ROADS PROGRAM Bureau of Indian Affairs Management Systems § 973.210 Indian lands bridge management system (BMS...

  7. 23 CFR 973.214 - Indian lands congestion management system (CMS).

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Indian lands congestion management system (CMS). 973.214... HIGHWAYS MANAGEMENT SYSTEMS PERTAINING TO THE BUREAU OF INDIAN AFFAIRS AND THE INDIAN RESERVATION ROADS PROGRAM Bureau of Indian Affairs Management Systems § 973.214 Indian lands congestion management system...

  8. Circulating miR-1, miR-133a, and miR-206 levels are increased after a half-marathon run.

    Science.gov (United States)

    Gomes, Clarissa P C; Oliveira, Getúlio P; Madrid, Bibiano; Almeida, Jeeser A; Franco, Octávio L; Pereira, Rinaldo W

    2014-11-01

    Circulating miRNAs are potential biomarkers that can be important molecules driving cell-to-cell communication. To investigate circulating muscle-specific miRNAs in recreational athletes. Three miRNAs from whole plasma before and after a half-marathon were analyzed by qPCR. MiR-1, -133a, and -206 significantly increased after the race. Increased levels of miRNAs after exercise point to potential biomarkers and to the possibility of being functional players following endurance training. These miRNAs are potential biomarkers of muscle damage or adaptation to exercise.

  9. Evaluating the Intraspecific Interactions of Indian Rosewood (Dalbergia sissoo Roxb. Trees in Indian Rosewood Reserveof Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Y. Erfanifard

    2016-05-01

    Full Text Available Positive and negative (facilitative and competitive interactions of plants are important issues in autecology and can be evaluated by the spatial pattern analysis in plant ecosystems. This study investigates the intraspecific interactions of Indian rosewood (Dalbergia sissoo Roxb. trees in Indian rosewood Reserve of Khuzestan province. Three 150 m × 200 m plots were selected and the spatial locations of all Indian rosewoods (239 trees were specified. Structurally different summary statistics (nearest neighbour distribution function D(r, K2-index K2(r, pair correlation function g(r, and O-ring O(r were also implemented to analyze the spatial pattern of the trees. The distribution of Indian rosewood trees significantly followed inhomogeneous Poisson process (α=0.05. The results of D(r and K2(r showed that the maximum distance to nearest tree was 12 m and density was decreased to this scale. The results of g(r and O(r also revealed the significant aggregation of Indian rosewood trees at scales of 1.5 to 4 m (α=0.05. In general, it was concluded that Indian rosewood trees had positive intraspecific interactions in Indian rosewood Reserve of Khuzestan province and their aggregation showed their facilitative effects on one another.

  10. miRNAtools: Advanced Training Using the miRNA Web of Knowledge.

    Science.gov (United States)

    Stępień, Ewa Ł; Costa, Marina C; Enguita, Francisco J

    2018-02-16

    Micro-RNAs (miRNAs) are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped the development not only of many computer applications for the prediction of miRNA target recognition but also of specific applications for functional assessment and analysis. Learning about miRNA function requires practical training in the use of specific computer and web-based applications that are complementary to wet-lab studies. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu), a web repository of miRNA tools and tutorials. This article compiles tools with which miRNAs and their regulatory action can be analyzed and that function to collect and organize information dispersed on the web. The miRNAtools website contains a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials engage in analyses of the functions of selected miRNAs, starting with their nomenclature and genomic localization and finishing with their involvement in specific cellular functions.

  11. Suppression of nemo-like kinase by miR-71 in Echinococcus multilocularis.

    Science.gov (United States)

    Guo, Xiaola; Zhang, Xueyong; Yang, Jing; Jin, Xiaoliang; Ding, Juntao; Xiang, Haitao; Ayaz, Mazhar; Luo, Xuenong; Zheng, Yadong

    2017-12-01

    Echinococcus multilocularis metacestodes are a causative pathogen for alveolar echinococcosis in human beings, and have been found to express miRNAs including emu-miR-71. miR-71 is evolutionarily conserved and highly expressed across platyhelminths, but little is known about its role. Here it was shown that emu-miR-71 was differentially expressed in protoscoleces and was unlikely to be expressed in neoblasts. The results of the luciferase assay indicated that emu-miR-71 was able to bind in vitro to the 3'-UTR of emu-nlk, encoding a key regulator of cell division, causing significant downregulation of luciferase activity (p < 0.01) compared to the negative control and the construct with mutations in the binding site. Consistent with the decreased luciferase activity, transfection of emu-miR-71 mimics into protoscoleces notably repressed emu-NLK (p < 0.05). These results demonstrate the suppression of emu-nlk by emu-miR-71, potentially involved in the protoscolex development. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Positive Gene Regulation by a Natural Protective miRNA Enables Arbuscular Mycorrhizal Symbiosis.

    Science.gov (United States)

    Couzigou, Jean-Malo; Lauressergues, Dominique; André, Olivier; Gutjahr, Caroline; Guillotin, Bruno; Bécard, Guillaume; Combier, Jean-Philippe

    2017-01-11

    Arbuscular mycorrhizal (AM) symbiosis associates most plants with fungi of the phylum Glomeromycota. The fungus penetrates into roots and forms within cortical cell branched structures called arbuscules for nutrient exchange. We discovered that miR171b has a mismatched cleavage site and is unable to downregulate the miR171 family target gene, LOM1 (LOST MERISTEMS 1). This mismatched cleavage site is conserved among plants that establish AM symbiosis, but not in non-mycotrophic plants. Unlike other members of the miR171 family, miR171b stimulates AM symbiosis and is expressed specifically in root cells that contain arbuscules. MiR171b protects LOM1 from negative regulation by other miR171 family members. These findings uncover a unique mechanism of positive post-transcriptional regulation of gene expression by miRNAs and demonstrate its relevance for the establishment of AM symbiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. miR-371, miR-138, miR-544, miR-145, and miR-214 could modulate Th1/Th2 balance in asthma through the combinatorial regulation of Runx3.

    Science.gov (United States)

    Qiu, Yu-Ying; Zhang, Ying-Wei; Qian, Xiu-Fen; Bian, Tao

    2017-01-01

    Asthma is tightly related to the imbalance of Th1/Th2 cells, and Runx3 plays a pivotal role in the differentiation of T helper cells. The present study aimed to investigate dysregulated microRNAs that may target Runx3 in CD4 + T cells from asthmatic patients and reveal Runx3 function in Th1/Th2 balance regulation. We detected the levels of Th1- and Th2-related cytokines by ELISA and analyzed the differentiation marker gene of T helper cells by qRT-PCR. Results indicated that an imbalance of Th1/Th2 cells was present in our asthmatic subject. Runx3 expression was reduced in the CD4 + T cells from asthmatic patients. Overexpression of Runx3 could restore the Th1/Th2 balance. After performing microRNA microarray assay, we found a series of microRNAs that were considerably altered in the CD4 + T cells from asthmatic patients. Among these upregulated microRNAs, eight microRNAs that may target Runx3 were selected by bioinformatics prediction. Five microRNAs, namely miR-371, miR-138, miR-544, miR-145, and miR-214, were confirmed by qRT-PCR and selected as candidate microRNAs. Luciferase reporter assay showed that these five microRNAs could directly target the 3'-UTR of Runx3. However, only simultaneous inhibition of these five microRNAs could alter the expression of Runx3. Most importantly, only simultaneous inhibition could improve the Th1/Th2 balance. Thus, we suggest that miR-371, miR-138, miR-544, miR-145, and miR-214 can modulate the Th1/Th2 balance in asthma by regulating Runx3 in a combinatorial manner.

  14. HAMDA: Hybrid Approach for MiRNA-Disease Association prediction.

    Science.gov (United States)

    Chen, Xing; Niu, Ya-Wei; Wang, Guang-Hui; Yan, Gui-Ying

    2017-12-01

    For decades, enormous experimental researches have collectively indicated that microRNA (miRNA) could play indispensable roles in many critical biological processes and thus also the pathogenesis of human complex diseases. Whereas the resource and time cost required in traditional biology experiments are expensive, more and more attentions have been paid to the development of effective and feasible computational methods for predicting potential associations between disease and miRNA. In this study, we developed a computational model of Hybrid Approach for MiRNA-Disease Association prediction (HAMDA), which involved the hybrid graph-based recommendation algorithm, to reveal novel miRNA-disease associations by integrating experimentally verified miRNA-disease associations, disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity into a recommendation algorithm. HAMDA took not only network structure and information propagation but also node attribution into consideration, resulting in a satisfactory prediction performance. Specifically, HAMDA obtained AUCs of 0.9035 and 0.8395 in the frameworks of global and local leave-one-out cross validation, respectively. Meanwhile, HAMDA also achieved good performance with AUC of 0.8965 ± 0.0012 in 5-fold cross validation. Additionally, we conducted case studies about three important human cancers for performance evaluation of HAMDA. As a result, 90% (Lymphoma), 86% (Prostate Cancer) and 92% (Kidney Cancer) of top 50 predicted miRNAs were confirmed by recent experiment literature, which showed the reliable prediction ability of HAMDA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Potential role of miR-9 and miR-223 in recurrent ovarian cancer

    Directory of Open Access Journals (Sweden)

    McGuinness Eamonn

    2008-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease. Results Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6 in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18 and FFPE serous ovarian tumours (n = 22. Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry. Conclusion We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.

  16. Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4⁺ T cells and peripheral blood from tuberculosis patients.

    Science.gov (United States)

    Kleinsteuber, Katja; Heesch, Kerrin; Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M; Jacobsen, Marc

    2013-01-01

    The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4(+) T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4(+) T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease.

  17. Targeting miRNAs by polyphenols: Novel therapeutic strategy for cancer.

    Science.gov (United States)

    Pandima Devi, Kasi; Rajavel, Tamilselvam; Daglia, Maria; Nabavi, Seyed Fazel; Bishayee, Anupam; Nabavi, Seyed Mohammad

    2017-10-01

    In the recent years, polyphenols have gained significant attention in scientific community owing to their potential anticancer effects against a wide range of human malignancies. Epidemiological, clinical and preclinical studies have supported that daily intake of polyphenol-rich dietary fruits have a strong co-relationship in the prevention of different types of cancer. In addition to direct antioxidant mechanisms, they also regulate several therapeutically important oncogenic signaling and transcription factors. However, after the discovery of microRNA (miRNA), numerous studies have identified that polyphenols, including epigallocatechin-3-gallate, genistein, resveratrol and curcumin exert their anticancer effects by regulating different miRNAs which are implicated in all the stages of cancer. MiRNAs are short, non-coding endogenous RNA, which silence the gene functions by targeting messenger RNA (mRNA) through degradation or translation repression. However, cancer associated miRNAs has emerged only in recent years to support its applications in cancer therapy. Preclinical experiments have suggested that deregulation of single miRNA is sufficient for neoplastic transformation of cells. Indeed, the widespread deregulation of several miRNA profiles of tumor and healthy tissue samples revealed the involvement of many types of miRNA in the development of numerous cancers. Hence, targeting the miRNAs using polyphenols will be a novel and promising strategy in anticancer chemotherapy. Herein, we have critically reviewed the potential applications of polyphenols on various human miRNAs, especially which are involved in oncogenic and tumor suppressor pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766-3p) and their potential targets in peripheral blood from vitiligo patients.

    Science.gov (United States)

    Shang, Zhiwei; Li, Hongwen

    2017-10-01

    Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune destruction of melanocytes is thought to be major factor in the etiology of vitiligo. miRNA-based regulators of gene expression have been reported to play crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA expressions and predict their potential targets, assessing the biological functions of differentially expressed miRNA. Total RNA was extracted from peripheral blood of vitiligo (experimental group, n = 5) and non-vitiligo (control group, n = 5) age-matched patients. Samples were hybridized to a miRNA array. Box, scatter and principal component analysis plots were performed, followed by unsupervised hierarchical clustering analysis to classify the samples. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted for validation of microarray data. Three different databases, TargetScan, PITA and microRNA.org, were used to predict the potential target genes. Gene ontology (GO) annotation and pathway analysis were performed to assess the potential functions of predicted genes of identified miRNA. A total of 100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot analysis. Four miRNA were validated by quantitative RT-PCR as significantly downregulated in the vitiligo group. The functions of predicted target genes associated with differentially expressed miRNA were assessed by GO analysis, showing that the GO term with most significantly enriched target genes was axon guidance, and that the axon guidance pathway was most significantly correlated with these miRNA. In conclusion, we identified four downregulated miRNA in vitiligo and assessed the potential functions of target genes related to these differentially expressed miRNA. © 2017 Japanese Dermatological Association.

  19. Myostatin regulates miR-431 expression via the Ras-Mek-Erk signaling pathway.

    Science.gov (United States)

    Wu, Rimao; Li, Hu; Li, Tingting; Zhang, Yong; Zhu, Dahai

    2015-05-29

    MicroRNAs (miRNAs) play critical regulatory roles in controlling myogenic development both in vitro and in vivo; however, the molecular mechanisms underlying transcriptional regulation of miRNA genes in skeletal muscle cells are largely unknown. Here, using a microarray hybridization approach, we identified myostatin-regulated miRNA genes in skeletal muscle tissues by systematically searching miRNAs that are differentially expressed between wild-type and myostatin-null mice during development. We found that 116 miRNA genes were differentially expressed in muscles between these mice across different developmental stages. We further characterized myostatin-regulated miR-431 was upregulated in skeletal muscle tissues of myostatin-null mice. In functional studies, we found that overexpression of miR-431 in C2C12 myoblast cells attenuated myostatin-induced suppression of myogenic differentiation. Mechanistic studies further demonstrated that myostatin acted through the Ras-Mek-Erk signaling pathway to transcriptionally regulate miR-431 expression C2C12 cells. Our findings provide new insight into the mechanisms underlying transcriptional regulation of miRNA genes by myostatin during skeletal muscle development. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Surviving as Indians: the challenge of self-government

    National Research Council Canada - National Science Library

    Boldt, Menno

    1993-01-01

    ... Canadians; Indian leadership that is committed to eliminating the colonial political and bureaucratic structures on their reserves, and returning Indian government into the hands of their people...

  1. Involvement of miR-485-5p in hepatocellular carcinoma progression targeting EMMPRIN.

    Science.gov (United States)

    Sun, Xiangjun; Liu, Yonglei; Li, Ming; Wang, Mingchun; Wang, Yutong

    2015-05-01

    EMMPRIN plays important roles in cancer development, which includes EMMPRIN 1, 2, 3, and 4 isoforms. EMMPRIN2 is the main component in human cancers, but its regulation by miRNAs is still unclear. In this study, we will investigate the mechanism of EMMPRIN regulation in hepatocellular carcinoma (HCC) by miRNAs. Through RT-PCR, we found that EMMPRIN2 was the main isoform in HCC cells. EMMPRIN2 was down-regulated significantly by predicted miRNAs and miR-485-5p was one of the miRNA that regulated EMMPRIN in HCC cell lines. It was verified that EMMPRIN was a target gene of miR-485-5p by using luciferase analysis assay. We found that miR-485-5p was significantly downregulated in HCC tissues and that its expression was inversely correlated with the TNM stage and metastasis in HCC samples. Results of cellular functions in HCC showed that miR-485-5p could inhibit cell proliferation and metastasis. Additionally, miR-485-5p overexpression suppressed HCC growth in vivo by down-regulation of EMMPRIN. Our study for the first time demonstrated that miR-485-5p represses HCC invasive and metastatic capacities by targeting EMMPRIN expression. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  3. Identification and validation of Asteraceae miRNAs by the expressed sequence tag analysis.

    Science.gov (United States)

    Monavar Feshani, Aboozar; Mohammadi, Saeed; Frazier, Taylor P; Abbasi, Abbas; Abedini, Raha; Karimi Farsad, Laleh; Ehya, Farveh; Salekdeh, Ghasem Hosseini; Mardi, Mohsen

    2012-02-10

    MicroRNAs (miRNAs) are small non-coding RNA molecules that play a vital role in the regulation of gene expression. Despite their identification in hundreds of plant species, few miRNAs have been identified in the Asteraceae, a large family that comprises approximately one tenth of all flowering plants. In this study, we used the expressed sequence tag (EST) analysis to identify potential conserved miRNAs and their putative target genes in the Asteraceae. We applied quantitative Real-Time PCR (qRT-PCR) to confirm the expression of eight potential miRNAs in Carthamus tinctorius and Helianthus annuus. We also performed qRT-PCR analysis to investigate the differential expression pattern of five newly identified miRNAs during five different cotyledon growth stages in safflower. Using these methods, we successfully identified and characterized 151 potentially conserved miRNAs, belonging to 26 miRNA families, in 11 genus of Asteraceae. EST analysis predicted that the newly identified conserved Asteraceae miRNAs target 130 total protein-coding ESTs in sunflower and safflower, as well as 433 additional target genes in other plant species. We experimentally confirmed the existence of seven predicted miRNAs, (miR156, miR159, miR160, miR162, miR166, miR396, and miR398) in safflower and sunflower seedlings. We also observed that five out of eight miRNAs are differentially expressed during cotyledon development. Our results indicate that miRNAs may be involved in the regulation of gene expression during seed germination and the formation of the cotyledons in the Asteraceae. The findings of this study might ultimately help in the understanding of miRNA-mediated gene regulation in important crop species. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Preliminary assessment of the water resources of the Tulalip Indian Reservation, Washington

    Science.gov (United States)

    Drost, B.W.

    1977-01-01

    In 1974 about 30 percent of the nearly 600 acre-feet of water used on the Tulalip Indian Reservation, Washington, was obtained from a surface-water reservoir, while nearly 70 percent was obtained from ground-water sources. Domestic use accounted for about 93 percent of total water use. Nutrient (phosphorus) concentrations measured in most surface-water samples were less than the maximum limit recommended by the U.S. Environmental Protection Agency. The recommended maximum limit for total coliform bacteria was never exceeded. Ground water is withdrawn from aquifers in unconsolidated deposits. Shallow aquifers, which provide about 45 percent of the total ground-water supply, are tapped by about 250 wells and yield 5 to 20 gpm to 30- and 42-inch diameter dug wells. Deeper aquifers yield about 55 percent of the ground-water supply to about 125 wells that are mostly between 100 and 150 feet deep. Yields are generally at least 20 gpm to 6- and 8-inch wells, and several wells have yields exceeding 300 gpm. Water in the shallow aquifers generally had an excessive concentration of dissolved iron, often exceeding the recommended maximum limit of 0.30 mg/liter, and total coliform bacteria in water from six wells exceeded 1 colony per 100 milliliters of water. Some wells in the deeper aquifers yield water with dissolved iron and (or) manganese concentrations exceeding the recommended maximum limit of 0.30 and 0.05 mg/liter, respectively. Although many deep coastal wells bottom far below sea level, only two wells indicated local saltwater intrusion. An aquifer underlying the central plateau and an artesian aquifer in the northeastern part of the reservation appear to offer the best potential for development of additional ground-water supplies. (Woodard-USGS)

  5. miRNA778 and SUVH6 are involved in phosphate homeostasis in Arabidopsis.

    Science.gov (United States)

    Wang, Lei; ZengJ, Hou Qing; Song, Jun; Feng, Sheng Jun; Yang, Zhi Min

    2015-09-01

    microRNAs (miRNAs) play an important role in plant adaptation to phosphate (Pi) starvation. Histone methylation can remodel chromatin structure and mediate gene expression. This study identified Arabidopsis miR778, a Pi-responsive miRNA, and its target gene Su(var) 3-9 homologs 6 (SUVH6) encoding a histone H3 lysine 9 (H3K9) methyltransferase. Overexpression of miR778 moderately enhanced primary and lateral root growth, free phosphate accumulation in shoots, and accumulation of anthocyanin under Pi deficient conditions. miR778 overexpression relieved the arrest of columella cell development under Pi starvation. Conversely, transgenic plants overexpressing a miR778-target mimic (35S::MIM778), that act as a sponge and sequesters miR778, showed opposite phenotypes of 35S::miR778 plants under Pi deficiency. Expression of several Pi deficiency-responsive genes such as miR399, Phosphate Transporter (PHT1;4), Low Phosphate-Resistant1 (LPR1) and Production of Anthocyanin Pigment 1 (PAP1) were elevated in the miR778 overexpressing plants, suggesting that both miR778 and SUVH6 are involved in phosphate homeostasis in plants. This study has provided a basis for further investigation on how SUVH6 regulates its downstream genes through chromatin remodeling and DNA methylation in plants stressed by Pi deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine

    2015-01-01

    analyses identified miR-21 as an independent prognostic marker for DSS in EAC [HR 3.52 (95% CI 1.06-11.69)]. High miR-375 was not correlated with improved prognosis in either histology. However, Forest plots demonstrated that both miR-21 and miR-375 were of prognostic impact in ESCC. CONCLUSION...... chemotherapy were analyzed. Expression levels of miR-21 and miR-375 were quantified using Affymetrix GeneChip miRNA 1.0 Array. The Cox proportional hazards model was used to assess the correlation of miR-21 and miR-375 with disease-specific survival (DSS) and overall survival (OS). Forest plots were performed...... to evaluate the prognostic impact of miR-21 and miR-375 in the present study and previously published reports. RESULTS: In ESCC, patients with miR-21 expression levels above median showed a trend towards poorer DSS and OS. When dividing miR-21 expression by tertiles, high levels of miR-21 significantly...

  7. High-throughput identification of miRNAs of Taenia ovis, a cestode threatening sheep industry.

    Science.gov (United States)

    Zheng, Yadong

    2017-07-01

    Taenia ovis is a tapeworm that is mainly transmitted between dogs and sheep or goats and has an adverse effect on sheep industry. miRNAs are short regulatory non-coding RNAs, involved in parasite development and growth as well as parasite infection. The miRNA profile of T. ovis remains to be established. Herein, 33 known miRNAs belonging to 23 different families were identified in T. ovis metacestodes using deep sequencing approach. Of them, expression of some miRNAs such as tov-miR-10 and -let-7 was absolutely predominant. Moreover, comparative analysis revealed the presence of a miR-71/2b/2c cluster in T. ovis, which was also completely conserved in other 6 cestodes. The study provides rich data for further understandings of T. ovis biology. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Early Sámi visual artists - Western fine art meets Sámi culture

    Directory of Open Access Journals (Sweden)

    Tuija Hautala-Hirvioja

    2014-04-01

    Full Text Available Johan Turi (1854–1936, Nils Nilsson Skum (1872–1951 and John Savio (1902–1938 were among the first Sámi visual artists. The production of their art work occurred between the 1910s and the early 1950s. Sámi aesthetics had its basis in folklore, i.e., handicraft or duodji, which did not follow the principle of art for art’s sake but combined beauty and practicality. Art was part of community life. Not until the 1970s was the word daidda, which is Finnish in origin and which means “art”, adopted into the Sámi language. Turi and Skum became famous through their books. They drew and wrote in order to pass the traditional knowledge of their people on to succeeding generations. They also wanted to introduce Sámi life and culture to non-Sámi people. One typical feature of their work is that they depicted Sáminess in a realistic way and sought to strengthen and preserve the Sámi identity through their art. In Turi and Skum’s work, both the documentation of community life and their own personal expression were strongly present and equally important; for this reason their pictures and texts have both practical and aesthetic dimensions. They did not attend school and were self-taught artists. The third pioneer of Sámi visual arts was John Savio, who, unlike the other two, attended secondary school and studied visual arts both independently and under the guidance of a mentor. He expressively combined Western ways of depiction with Sámi subjects. My article examines what made these early Sámi artists change over from Sámi handicraft, duodji, to Western visual arts, how they used Western pictorial conventions in dealing with their Sámi subjects, and the significance of their art for Sámi identity and culture. They lived and worked under cross pressure: the first few decades of the 20th century were characterized by racial theories that denigrated Sámi people, and the period following World War II was marked by demands for

  9. miR-181a and miR-630 regulate cisplatin-induced cancer cell death.

    Science.gov (United States)

    Galluzzi, Lorenzo; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Senovilla, Laura; Criollo, Alfredo; Servant, Nicolas; Paccard, Caroline; Hupé, Philippe; Robert, Thomas; Ripoche, Hugues; Lazar, Vladimir; Harel-Bellan, Annick; Dessen, Philippe; Barillot, Emmanuel; Kroemer, Guido

    2010-03-01

    MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not lethal when transfected into A549 cells yet affected cell death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs) targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP, pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death, respectively. Pre-miR-181a and pre-miR-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including Bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR-630 blocked early manifestations of the DNA damage response, including the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53 corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the upstream signaling pathways that are ignited by DNA damage and converge on p53 activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle, correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well as with reduced proliferation rates and resulting in greatly diminished sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP. Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC.

  10. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Andersen, Morten; Grauslund, Morten; Ravn, Jesper

    2014-01-01

    Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miR...

  11. 76 FR 9593 - Proclaiming Certain Lands, Reykers Acquisition, as an Addition to the Bay Mills Indian...

    Science.gov (United States)

    2011-02-18

    ..., as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan..., more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community of... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  12. 25 CFR 141.27 - Trade in imitation Indian crafts prohibited.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Trade in imitation Indian crafts prohibited. 141.27 Section 141.27 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES BUSINESS PRACTICES ON THE NAVAJO, HOPI AND ZUNI RESERVATIONS General Business Practices § 141.27 Trade in imitation...

  13. Identification and characterization of miRNAs transcriptome in the South African abalone, Haliotis midae.

    Science.gov (United States)

    Picone, Barbara; Rhode, Clint; Roodt-Wilding, Rouvay

    2017-02-01

    Aquatic animal diseases are one of the most important limitations to the growth of aquaculture. miRNAs represent an important class of small ncRNAs able to modulate host immune and stress responses. In Mollusca, a large phylum of invertebrates, miRNAs have been identified in several species. The current preliminary study identified known miRNAs from the South African abalone, Haliotis midae. The economic and ecological importance of abalone makes this species a suitable model for studying and understanding stress response in marine gastropods. Furthermore, the identification of miRNA, represents an alternative and powerful tool to combat infectious disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.

    Science.gov (United States)

    Wang, Shanshan; Wang, Jun; Zhang, Zengdi; Miao, Hongjun

    2017-08-01

    Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

  15. Relationship of psychosocial risk factors, certain personality traits and myocardial infarction in Indians: A case-control study

    Directory of Open Access Journals (Sweden)

    Rajni Gupta

    2011-01-01

    Full Text Available Objective: To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being and personality traits with myocardial infarction (MI. Materials and Methods: A case-control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi. Results: Stress over 1 year was significantly higher in cases (P < 0.001. However, difference was not significant when scores of social support (P = 0.2, Presumptive Stressful Life Event (PSLE over lifetime (P = 0.058 and subjective well-being (P = 0.987 were compared. MI was significantly associated with hyperactive (P < 0.001, dominant (P = 0.03, egoistic (P < 0.001 and introvert (P < 0.001 personalities. Conclusion: Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients.

  16. Bioinformatic identification and experimental validation of miRNAs from foxtail millet (Setaria italica).

    Science.gov (United States)

    Han, Jun; Xie, Hao; Sun, Qingpeng; Wang, Jun; Lu, Min; Wang, Weixiang; Guo, Erhu; Pan, Jinbao

    2014-08-10

    MiRNAs are a novel group of non-coding small RNAs that negatively regulate gene expression. Many miRNAs have been identified and investigated extensively in plant species with sequenced genomes. However, few miRNAs have been identified in foxtail millet (Setaria italica), which is an ancient cereal crop of great importance for dry land agriculture. In this study, 271 foxtail millet miRNAs belonging to 44 families were identified using a bioinformatics approach. Twenty-three pairs of sense/antisense miRNAs belonging to 13 families, and 18 miRNA clusters containing members of 8 families were discovered in foxtail millet. We identified 432 potential targets for 38 miRNA families, most of which were predicted to be involved in plant development, signal transduction, metabolic pathways, disease resistance, and environmental stress responses. Gene ontology (GO) analysis revealed that 101, 56, and 23 target genes were involved in molecular functions, biological processes, and cellular components, respectively. We investigated the expression patterns of 43 selected miRNAs using qRT-PCR analysis. All of the miRNAs were expressed ubiquitously with many exhibiting different expression levels in different tissues. We validated five predicted targets of four miRNAs using the RNA ligase mediated rapid amplification of cDNA end (5'-RLM-RACE) method. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. MiR-598: A tumor suppressor with biomarker significance in osteosarcoma.

    Science.gov (United States)

    Liu, Kai; Sun, Xiaolu; Zhang, Yingang; Liu, Liang; Yuan, Qiling

    2017-11-01

    Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents. Identifying specific and sensitive biomarkers is beneficial to early detection and improvement of life qualities and overall survival rates of osteosarcoma patients. Realtime PCR was used to detect the expression of miR-598. CCK-8 assay was employed to detect the proliferation of osteosarcoma cells, while transwell assays were used to examine the migration and invasion. Tumor xenograft experiments were performed to test the in vivo malignancy of osteosarcoma cells. Co-culture experiment was used to study the relationship between osteosarcoma cells and osteoblast. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. Using a cohort of 20 cases of osteosarcoma and paired adjacent tissue samples, we found that miR-598 expression was decreased in osteosarcoma tissues and serum, as well as the osteosarcoma cell lines. Over expression of miR-598 suppressed the proliferation, migration, and invasion of osteosarcoma cells, while inhibition of miR-598 expression stimulated the proliferation, migration, and invasion. However, MiR-598 had no effect on osteosarcoma cell apoptosis. Data from nude mice further demonstrated the inhibitory role of miR-598 in osteosarcoma progression in vivo. Mechanically, miR-598 played its role by modulating osteoblastic differentiation in the microenvironment and targeting PDGFB and MET. Our findings enrich the knowledge of miR-598 in osteosarcoma progression, and reveal miR-598 as a promising diagnostic, prognostic, therapeutic biomarker for osteosarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Measurement of the Single Top Quark Production Cross Section and |<mi>Vtb>| in Events with One Charged Lepton, Large Missing Transverse Energy, and Jets at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d’Ascenzo, N.; Datta, M.; de Barbaro, P.; Demortier, L.; Deninno, M.; D’Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Galloni, C.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hirschbuehl, D.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Marchese, L.; Margaroli, F.; Marino, P.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; St. Denis, R.; Stancari, M.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Waters, D.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

    2014-12-31

    We report a measurement of single top quark production in proton-antiproton collisions at a center-of-mass energy of mi>s>=1.96 mi>TeV> using a data set corresponding to 7.5 mi>fb>-1 of integrated luminosity collected by the Collider Detector at Fermilab. We select events consistent with the single top quark decay process mi>t>mi>Wb>mi>νb> by requiring the presence of an electron or muon, a large imbalance of transverse momentum indicating the presence of a neutrino, and two or three jets including at least one originating from a bottom quark. An artificial neural network is used to discriminate the signal from backgrounds. We measure a single top quark production cross section of 3.04-0.53+0.57 mi>pb> and set a lower limit on the magnitude of the coupling between the top quark and bottom quark |mi>V

  19. miRNAs in brain development

    International Nuclear Information System (INIS)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function

  20. Cell type-specific deficiency of c-kit gene expression in mutant mice of mi/mi genotype.

    Science.gov (United States)

    Isozaki, K.; Tsujimura, T.; Nomura, S.; Morii, E.; Koshimizu, U.; Nishimune, Y.; Kitamura, Y.

    1994-01-01

    The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called mi factor). In addition to microphthalmus, osteopetrosis, and lack of melanocytes, mice of mi/mi genotype are deficient in mast cells. Since the c-kit receptor tyrosine kinase plays an important role in the development of mast cells, and since the c-kit expression by cultured mast cells from mi/mi mice is deficient in both mRNA and protein levels, the mast cell deficiency of mi/mi mice has been attributed at least in part to the deficient expression of c-kit. However, it remained to be examined whether the c-kit expression was also deficient in tissues of mi/mi mice. In the present study, we examined the c-kit expression by mi/mi skin mast cells using in situ hybridization and immunohistochemistry. Moreover, we examined the c-kit expression by various cells other than mast cells in tissues of mi/mi mice. We found that the c-kit expression was deficient in mast cells but not in erythroid precursors, testicular germ cells, and neurons of mi/mi mice. This suggested that the regulation of the c-kit transcription by the mi factor was dependent on cell types. Mice of mi/mi genotype appeared to be a useful model to analyze the function of transcription factors in the whole-animal level. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7524330

  1. 76 FR 2409 - Proclaiming Certain Lands, Golf Course Acquisition, as an Addition to the Bay Mills Indian...

    Science.gov (United States)

    2011-01-13

    ... Acquisition, as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan..., more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community of... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  2. 76 FR 52011 - Proclaiming Certain Lands, Forest Service Lands, as an Addition to the Bay Mills Indian...

    Science.gov (United States)

    2011-08-19

    ... Lands, as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan... acres, more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  3. 78 FR 65589 - Leasing of Osage Reservation Lands for Oil and Gas Mining

    Science.gov (United States)

    2013-11-01

    ... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs 25 CFR Part 226 [BIA-2013-0003; 134/A0A511010/AAK1001000] RIN 1076-AF17 Leasing of Osage Reservation Lands for Oil and Gas Mining AGENCY: Bureau of Indian... oil and gas mining on reservation land of the Osage Nation. The public comment period for that rule...

  4. miRNAFold: a web server for fast miRNA precursor prediction in genomes.

    Science.gov (United States)

    Tav, Christophe; Tempel, Sébastien; Poligny, Laurent; Tahi, Fariza

    2016-07-08

    Computational methods are required for prediction of non-coding RNAs (ncRNAs), which are involved in many biological processes, especially at post-transcriptional level. Among these ncRNAs, miRNAs have been largely studied and biologists need efficient and fast tools for their identification. In particular, ab initio methods are usually required when predicting novel miRNAs. Here we present a web server dedicated for miRNA precursors identification at a large scale in genomes. It is based on an algorithm called miRNAFold that allows predicting miRNA hairpin structures quickly with high sensitivity. miRNAFold is implemented as a web server with an intuitive and user-friendly interface, as well as a standalone version. The web server is freely available at: http://EvryRNA.ibisc.univ-evry.fr/miRNAFold. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Sociocultural perspective on organ and tissue donation among reservation-dwelling American Indian adults.

    Science.gov (United States)

    Fahrenwald, Nancy L; Stabnow, Wendy

    2005-11-01

    To discover the sociocultural patterns that influence decisions about organ and tissue donation among American Indian (AI) adults. This qualitative ethnographic study used a social-ecological framework. A snowball sampling technique was used to recruit 21 Oglala Lakota Sioux participants (age >or= 19 years) living on the Pine Ridge Indian Reservation in South Dakota, USA. Face-to-face interviews were conducted using open-ended questions derived from the social-ecological perspective of Stokols (1992). Interviews were audiotaped and transcribed. Data were categorized into construct codes to identify concepts and to discover emerging themes. Personal and environmental themes regarding organ and tissue donation emerged. There were two personal themes: uncertain knowledge and the diabetes crisis. Participants knew very little about organ and tissue donation but there was a basic understanding of donor/recipient compatibility. The prevalence of diabetes in the community is contributing to a dire need for kidney donors. The diabetes crisis was acknowledged by every participant. There were three environmental themes: cultural transitions, healthcare system competence and outreach efforts. Traditional cultural beliefs such as entering the spirit world with an intact body were acknowledged. However, conversations reflected re-examination of traditional beliefs because of the need for kidney donors. The healthcare environmental context of organ and tissue donation emerged as a theme. Participants were not confident that the local health system was prepared to either address traditional beliefs about organ and tissue donation or implement a donation protocol. The final theme was the environmental context of outreach efforts. Participants desired relevant outreach targeted to the community and disseminated through local communication networks including the family, the media and tribal leaders. Sociocultural factors relevant to the personal and environmental context of the

  6. miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation.

    Science.gov (United States)

    Ban, Young Ho; Oh, Se-Chan; Seo, Sang-Hwan; Kim, Seok-Min; Choi, In-Pyo; Greenberg, Philip D; Chang, Jun; Kim, Tae-Don; Ha, Sang-Jun

    2017-09-12

    MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8 + T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8 + T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8 + T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8 + T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8 + T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Dysregulated miR-103 and miR-143 expression in peripheral blood mononuclear cells from induced prediabetes and type 2 diabetes rats.

    Science.gov (United States)

    Vatandoost, Nasimeh; Amini, Masoud; Iraj, Bijan; Momenzadeh, Sedigheh; Salehi, Rasoul

    2015-11-01

    The progression from normal glucose tolerance (NGT) to type 2 diabetes (T2D) occurs through an intermediate state of glucose intolerance known as pre-diabetes. This transition is usually a gradual phenomenon that occurs over 5-10 years. Among the routinely practiced T2D screening criteria, like, FPG, IFG, IGT or HbA1c, still the issue of a preferable one is debated. The newly emerged microRNAs are created much hope to act as a class of suitable diabetes gene signature detectable at an early stage of the disease development. Although T2D related miRNA fluctuations are reported from the main insulin target organs, sampling of these organs for the sake of screening due to its invasive nature is not practicable. Peripheral blood mononuclear cells (PBMCs) are in constant touch with all body organs hence may exhibit the trace of miRNA changes which take place in insulin target organs. In this study we have evaluated miR-103 and miR-143 expression in three groups of rats namely; normal control, high fat diet (HFD) which is corresponding to prediabetes state, and high fat diet/streptozotocin (STZ) induced T2D. Quantitative real time PCR was used for profiling the selected miRNA expression at various time intervals of the three defined groups of rats. In prediabetes and overt diabetes stages, miR-103 showed significantly elevated expression in PBMC specimens compared to the normal healthy control group. Overexpression pattern of mir-143 was statistically significant in T2D compared to non-diabetic controls. However in HFD (prediabetic) rats also we observed an increasing pattern of miR-143 compared to the normal controls but it was not statistically significant. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome.

    Science.gov (United States)

    Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

    2010-11-27

    MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs.

  9. Assessing Differences in the Availability of Opioid Addiction Therapy Options: Rural Versus Urban and American Indian Reservation Versus Nonreservation.

    Science.gov (United States)

    Hirchak, Katherine A; Murphy, Sean M

    2017-01-01

    Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use disorder therapy. Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. The unit of analysis was the ZIP code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18-64 in a ZIP code. A region was defined as a ZIP code and its contiguous ZIP codes. The independent variables were binary measures of whether a ZIP code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. The number of OAT clinics in a region per 10,000 ZIP-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 ZIP-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. © 2016 National Rural Health Association.

  10. Indian Summer

    Energy Technology Data Exchange (ETDEWEB)

    Galindo, E. [Sho-Ban High School, Fort Hall, ID (United States)

    1997-08-01

    This paper focuses on preserving and strengthening two resources culturally and socially important to the Shoshone-Bannock Indian Tribe on the Fort Hall Reservation in Idaho; their young people and the Pacific-Northwest Salmon. After learning that salmon were not returning in significant numbers to ancestral fishing waters at headwater spawning sites, tribal youth wanted to know why. As a result, the Indian Summer project was conceived to give Shoshone-Bannock High School students the opportunity to develop hands-on, workable solutions to improve future Indian fishing and help make the river healthy again. The project goals were to increase the number of fry introduced into the streams, teach the Shoshone-Bannock students how to use scientific methodologies, and get students, parents, community members, and Indian and non-Indian mentors excited about learning. The students chose an egg incubation experiment to help increase self-sustaining, natural production of steelhead trout, and formulated and carried out a three step plan to increase the hatch-rate of steelhead trout in Idaho waters. With the help of local companies, governmental agencies, scientists, and mentors students have been able to meet their project goals, and at the same time, have learned how to use scientific methods to solve real life problems, how to return what they have used to the water and land, and how to have fun and enjoy life while learning.

  11. miR-494 represses HOXA10 expression and inhibits cell proliferation in oral cancer.

    Science.gov (United States)

    Libório-Kimura, Tatiana N; Jung, Hyun Min; Chan, Edward K L

    2015-02-01

    miR-494 was identified as a candidate of the most significantly underexpressed microRNAs (miRNAs) in our oral cancer screen. The aim of this study was to validate whether miR-494 has a functional role in oral cancer. Quantitative miRNA analyses were performed on oral tumor RNA and oral cancer cell lines. HOXA10 was selected for further analysis based on bioinformatics analysis of miR-494 targets and a previous report of overexpression of HOXA10 in oral cancer. Transient transfection of miRNA-mimic and inhibitor were performed in SCC-25 (tongue), CAL 27 (tongue), and FaDu (pharynx) cancer cells and regulation of HOXA10 by miR-494 was investigated. Dual luciferase assay was used to verify the interaction between miR-494 and HOXA10 in reporter cells. The effect of miR-494 on cell proliferation was examined. Our data showed that miR-494 was underexpressed whereas HOXA10 was overexpressed in oral cancer compared to normal tissues. An inverse correlation between miR-494 and HOXA10 was observed in the human tissues (pcancer cell lines significantly reduced the expression of HOXA10 mRNA. The luciferase reporter that contains the 3'UTR of HOXA10 showed a significantly reduced luciferase activity by miR-494 indicating a direct interaction between HOXA10 and miR-494. Significant reduction in cell proliferation was demonstrated in tongue cancer cells transfected with miR-494. miR-494 repressed the expression of HOXA10 and also reduced the proliferation of oral cancer cells. These data give more evidence of the role of miR-494 as a tumor suppressor miRNA in oral cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Perspectives on Sámi historiography

    Directory of Open Access Journals (Sweden)

    Lars Ivar Hansen

    2017-09-01

    Full Text Available The article focuses on Sámi history and historical methods. The main results and central aspects of Sámi history, in its relational context, are gone through. What effects and consequences — regarding both methodology and narrative styles — these aspects have had, and ought to have, for the processes of doing research on and writing Sámi history? The focus is on the politics of Sámi history and research. The issues, who is “allowed” to write Sámi history and the way Sámi research is demanded to stand in the service of different societal-cultural needs of the Sámi is dealt with. This expectation of applicability concerns Sámi history in general, and the more delimited efforts of presenting situated accounts of Sámi cultural practices, traditions and experience with relations to other folk groups. Finally, methodological considerations and recommendations of Sámi history are presented, in which a number of methodological competences and in-depth usage of numerous source categories are called for.

  13. Measurement of Ratios of <mi>νμ> Charged-Current Cross Sections on C, Fe, and Pb to CH at Neutrino Energies 2–20 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Tice, B. G.; Datta, M.; Mousseau, J.; Aliaga, L.; Altinok, O.; Barrios Sazo, M. G.; Betancourt, M.; Bodek, A.; Bravar, A.; Brooks, W. K.; Budd, H.; Bustamante, M. J.; Butkevich, A.; Martinez Caicedo, D. A.; Castromonte, C. M.; Christy, M. E.; Chvojka, J.; da Motta, H.; Devan, J.; Dytman, S. A.; Díaz, G. A.; Eberly, B.; Felix, J.; Fields, L.; Fiorentini, G. A.; Gago, A. M.; Gallagher, H.; Gran, R.; Harris, D. A.; Higuera, A.; Hurtado, K.; Jerkins, M.; Kafka, T.; Kordosky, M.; Kulagin, S. A.; Le, T.; Maggi, G.; Maher, E.; Manly, S.; Mann, W. A.; Marshall, C. M.; Martin Mari, C.; McFarland, K. S.; McGivern, C. L.; McGowan, A. M.; Miller, J.; Mislivec, A.; Morfín, J. G.; Muhlbeier, T.; Naples, D.; Nelson, J. K.; Norrick, A.; Osta, J.; Palomino, J. L.; Paolone, V.; Park, J.; Patrick, C. E.; Perdue, G. N.; Rakotondravohitra, L.; Ransome, R. D.; Ray, H.; Ren, L.; Rodrigues, P. A.; Savage, D. G.; Schellman, H.; Schmitz, D. W.; Simon, C.; Snider, F. D.; Solano Salinas, C. J.; Tagg, N.; Valencia, E.; Velásquez, J. P.; Walton, T.; Wolcott, J.; Zavala, G.; Zhang, D.; Ziemer, B. P.

    2014-06-01

    We present measurements of mi>νμ> charged-current cross section ratios on carbon, iron, and lead relative to a scintillator (CH) using the fine-grained MINERvA detector exposed to the NuMI neutrino beam at Fermilab. The measurements utilize events of energies 2<mi>Eν><20mi>GeVmi>, with (mi>Eν>)=8mi>GeV>, which have a reconstructed mi>μ>- scattering angle less than 17° to extract ratios of inclusive total cross sections as a function of neutrino energy mi>Eν> and flux-integrated differential cross sections with respect to the Bjorken scaling variable mi>x>. These results provide the first high-statistics direct measurements of nuclear effects in neutrino scattering using different targets in the same neutrino beam. Measured cross section ratios exhibit a relative

  14. Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

    Science.gov (United States)

    Takeda, Toru; Tanabe, Hiroyuki

    2016-03-18

    The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. School Shootings Stun Reservation

    Science.gov (United States)

    Borja, Rhea R.; Cavanagh, Sean

    2005-01-01

    This article deals with the impact brought by the school shootings at Red Lake Indian Reservation in Minnesota to the school community. A deeply troubled 16-year-old student shot and killed seven other people and himself at a high school. The nation's deadliest school attack since the 1999 slayings at Colorado's suburban Columbine High School took…

  16. MiR-34a/miR-93 target c-Ski to modulate the proliferaton of rat cardiac fibroblasts and extracellular matrix deposition in vivo and in vitro.

    Science.gov (United States)

    Zhang, Chengliang; Zhang, Yanfeng; Zhu, Hong; Hu, Jiajia; Xie, Zhongshang

    2018-06-01

    Cardiac fibrosis is associated with diverse heart diseases. In response to different pathological irritants, cardiac fibroblasts may be induced to proliferate and differentiate into cardiac myofibroblasts, thus contributing to cardiac fibrosis. TGF-β signaling is implicated in the development of heart failure through the induction of cardiac fibrosis. C-Ski, an inhibitory regulator of TGF-β signaling, has been reported to suppress TGF-β1-induced human cardiac fibroblasts' proliferation and ECM protein increase; however, the underlying molecular mechanism needs further investigation. In the present study, we demonstrated that c-Ski could ameliorate isoproterenol (ISO)-induced rat myocardial fibrosis model and TGF-β1-induced primary rat cardiac fibroblasts' proliferation, as well as extracellular matrix (ECM) deposition. The protein level of c-Ski was dramatically decreased in cardiac fibrosis and TGF-β1-stimulated primary rat cardiac fibroblasts. In recent decades, a family of small non-coding RNA, namely miRNAs, has been reported to regulate gene expression by interacting with diverse mRNAs and inducing either translational suppression or mRNA degradation. Herein, we selected miR-34a and miR-93 as candidate miRNAs that might target to regulate c-Ski expression. After confirming that miR-34a/miR-93 targeted c-Ski to inhibit its expression, we also revealed that miR-34a/miR-93 affected TGF-β1-induced fibroblasts' proliferation and ECM deposition through c-Ski. Taken together, we demonstrated a miR-34a/miR-93-c-Ski axis which modulates TGF-β1- and ISO-induced cardiac fibrosis in vitro and in vivo; targeting the inhibitory factors of c-Ski to rescue its expression may be a promising strategy for the treatment of cardiac fibrosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Molecular phylogeny of Hemidactylus geckos (Squamata: Gekkonidae) of the Indian subcontinent reveals a unique Indian radiation and an Indian origin of Asian house geckos.

    Science.gov (United States)

    Bansal, Rohini; Karanth, K Praveen

    2010-10-01

    Represented by approximately 85 species, Hemidactylus is one of the most diverse and widely distributed genera of reptiles in the world. In the Indian subcontinent, this genus is represented by 28 species out of which at least 13 are endemic to this region. Here, we report the phylogeny of the Indian Hemidactylus geckos based on mitochondrial and nuclear DNA markers sequenced from multiple individuals of widely distributed as well as endemic congeners of India. Results indicate that a majority of the species distributed in India form a distinct clade whose members are largely confined to the Indian subcontinent thus representing a unique Indian radiation. The remaining Hemidactylus geckos of India belong to two other geographical clades representing the Southeast Asian and West-Asian arid zone species. Additionally, the three widely distributed, commensal species (H. brookii, H. frenatus and H. flaviviridis) are nested within the Indian radiation suggesting their Indian origin. Dispersal-vicariance analysis also supports their Indian origin and subsequent dispersal out-of-India into West-Asian arid zone and Southeast Asia. Thus, Indian subcontinent has served as an important arena for diversification amongst the Hemidactylus geckos and in the evolution and spread of its commensal geckos. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Myositis-specific and myositis-associated autoantibodies in Indian patients with inflammatory myositis.

    Science.gov (United States)

    Srivastava, Puja; Dwivedi, Sanjay; Misra, Ramnath

    2016-07-01

    We aimed to study the prevalence and clinical associations of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in a large cohort of Indian patients with idiopathic inflammatory myositis (IIM). Clinical details and serum samples were collected from patients with IIM (satisfying Bohan and Peter Criteria, 1975) and CTD-associated myositis. Sera were analysed for antibodies against SRP, Mi2, Jo1, PL7, PL12, EJ, OJ, Ro52, Ku, Pm-Scl 75 and PM-Scl 100, using immunoblot assay. The cohort comprised 124 patients with IIM (M:F = 1:3.6). Fifty-five of them had dermatomyositis (DM), 22 had juvenile dermatomyositis (JDM), 25 had polymyositis (PM) and 22 had connective tissue disease-associated myositis (CTD myositis). Mean disease duration was 10.9 months. ANA was positive in 84 (68.9 %), and MSAs in 61 (49.2 %) patients. Among MSAs, autoantibodies to Mi2, synthetase (Jo1, PL7, PL12, EJ) and SRP were present in 26 (20.9 %), 29 (23.4 %) and 6 (4.8 %) patients, respectively. Prevalence of MAAs was as follows: antibodies to Ro52 in 45 (36.3 %), Ku and PM-Scl 75 in 13 (10.5 %) and PM-Scl 100 in 5 (4 %) patients. Anti-Mi2 antibodies were positively associated with DM (21/55, 38.2 %; p < 0.0001) and pharyngeal weakness (13/34, 38.2 %; p = 0.004) and negatively associated with ILD (0/28; p = 0.001). ILD and mechanics' hands were significantly more in patients with anti-synthetase antibodies (16/28, 57 % and 14/22, 63.6 %; p < 0.0001). Four of six patients with anti-SRP antibody showed poor response to multiple drugs. Higher prevalence of anti-Mi2 is probably related to higher proportion of patients with DM. Absence of ILD in patients with anti-Mi2 antibody suggests that it may protect against ILD. In Indian population also, anti-synthetase antibodies are associated with ILD, and anti-SRP antibodies with poor response to treatment.

  19. Knock-down of miR-221 and miR-222 in the radiosensitization of breast cancer cells

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Kang Chunsheng; Cao Yongzhen; Pu Peiyu; Lu Zhonghong; Du Yue

    2009-01-01

    Objective: To investigate the radiosensitizing effect of knock-down of miR-221 miR-222 on MCF-7 human breast cancer cells and explore the possible mechanism. Methods: Antisense oligonucleotides of miR-221 and miR-222 (AS-miR-221 and AS-miR-222), mediated by lipofectamine, were transfected to MCF-7 cells to knock down miR-221 and miR-222, Northern blotting was conducted to detect the expression of miR-221 and miR-222 in transfected cells. The cell apoptosis was detected by flow cytometry and Caspase-3 and Caspase-7 activity assay. Clonogenic assay was used to measure the sensitizing enhancement ratio. Target genes of miR-221 and miR-222 relevant to radio-sensitivity were searched using bioinformatics analysis. The targeted protein expression was determined by Western blot analysis. Results: The expression of miR-221 and miR-222 in the AS-miR-221/222 cells determined by Northern blotting was significantly reduced. Compared with the control group, the cell apoptosis and mitotic cell death after the radiation were significantly higher in AS-miR-221/222 cells. The sensitizing enhancement ratio was 1.87. Based on bioinformatics analysis, PTEN was a target gene of miR-221 and miR-222 which could enhance the radiosensitivity of MCF-7 cells. In AS-miR-221/222 cells, the expression of PTEN was up-regulated while pAkt down-regulated. Conclusions: AS-miR-221 and AS-miR-222 may enhance the radiosensitivity of MCF-7 breast cancer cells by up-regulating the expression of PTEN. (authors)

  20. Evidence for miRNA-mediated modulation of the host transcriptome in cnidarian-dinoflagellate symbiosis

    KAUST Repository

    Baumgarten, Sebastian

    2017-12-08

    Reef-building corals and other cnidarians living in symbiotic relationships with intracellular, photosynthetic dinoflagellates in the genus Symbiodinium undergo transcriptomic changes during infection with the algae and maintenance of the endosymbiont population. However, the precise regulatory mechanisms modulating the host transcriptome are unknown. Here we report apparent post-transcriptional gene regulation by miRNAs in the sea anemone Aiptasia, a model system for cnidarian-dinoflagellate endosymbiosis. Aiptasia encodes mainly species-specific miRNAs, and there appears to have been recent differentiation within the Aiptasia genome of miRNAs that are commonly conserved among anthozoan cnidarians. Analysis of miRNA expression showed that both conserved and species-specific miRNAs are differentially expressed in response to endosymbiont infection. Using cross-linking immunoprecipitation of Argonaute, the central protein of the miRNA-induced silencing complex, we identified miRNA binding sites on a transcriptome-wide scale and found that the targets of the miRNAs regulated in response to symbiosis include genes previously implicated in biological processes related to Symbiodinium infection. Our study shows that cnidarian miRNAs recognize their mRNA targets via high-complementarity target binding and suggests that miRNA-mediated modulations of genes and pathways are important during the onset and maintenance of cnidarian-dinoflagellate endosymbiosis. This article is protected by copyright. All rights reserved.

  1. Evidence for miRNA-mediated modulation of the host transcriptome in cnidarian-dinoflagellate symbiosis

    KAUST Repository

    Baumgarten, Sebastian; Cziesielski, Maha J.; Thomas, Ludivine; Michell, Craig; Esherick, Lisl Y.; Pringle, John R.; Aranda, Manuel; Voolstra, Christian R.

    2017-01-01

    Reef-building corals and other cnidarians living in symbiotic relationships with intracellular, photosynthetic dinoflagellates in the genus Symbiodinium undergo transcriptomic changes during infection with the algae and maintenance of the endosymbiont population. However, the precise regulatory mechanisms modulating the host transcriptome are unknown. Here we report apparent post-transcriptional gene regulation by miRNAs in the sea anemone Aiptasia, a model system for cnidarian-dinoflagellate endosymbiosis. Aiptasia encodes mainly species-specific miRNAs, and there appears to have been recent differentiation within the Aiptasia genome of miRNAs that are commonly conserved among anthozoan cnidarians. Analysis of miRNA expression showed that both conserved and species-specific miRNAs are differentially expressed in response to endosymbiont infection. Using cross-linking immunoprecipitation of Argonaute, the central protein of the miRNA-induced silencing complex, we identified miRNA binding sites on a transcriptome-wide scale and found that the targets of the miRNAs regulated in response to symbiosis include genes previously implicated in biological processes related to Symbiodinium infection. Our study shows that cnidarian miRNAs recognize their mRNA targets via high-complementarity target binding and suggests that miRNA-mediated modulations of genes and pathways are important during the onset and maintenance of cnidarian-dinoflagellate endosymbiosis. This article is protected by copyright. All rights reserved.

  2. 23 CFR 973.212 - Indian lands safety management system (SMS).

    Science.gov (United States)

    2010-04-01

    ... implementation of public information and education activities on safety needs, programs, and countermeasures... 23 Highways 1 2010-04-01 2010-04-01 false Indian lands safety management system (SMS). 973.212... HIGHWAYS MANAGEMENT SYSTEMS PERTAINING TO THE BUREAU OF INDIAN AFFAIRS AND THE INDIAN RESERVATION ROADS...

  3. Evaluation of miR-182/miR-100 Ratio for Diagnosis and Survival Prediction in Bladder Cancer.

    Science.gov (United States)

    Chen, Zhanguo; Wu, Lili; Lin, Qi; Shi, Jing; Lin, Xiangyang; Shi, Liang

    2016-09-01

    Abnormal expression of microRNAs (miRNAs) plays an important role in development of several cancer types, including bladder cancer (BCa). However, the relationship between the ratio of miR-181/miR-100 and the prognosis of BCa has not been studied yet. The aim of this study was to evaluate the expression of miR-182, miR-100 and their clinical significance in BCa. Upregulation of miR-182 and down-regulation of miR-100 were validated in tissue specimens of 134 BCa cases compared with 148 normal bladder epithelia (NBE) specimens  using TaqMan-based real-time reverse transcription quantitative PCR (RT-qPCR). The diagnostic and prognostic evaluation of miR-182, miR-100, and miR-182/miR-100 ratio was also performed. miR-182 was upregulated in BCa and miR-100 was down-regulated in BCa compared with NBE (P ratio increased the diagnostic performance, yielding an AUC of 0.981 (97.01% sensitivity and 90.54% specificity). Moreover, miR-182/miR-100 ratio was associated with pT-stage, histological grade, BCa recurrence and carcinoma in situ (P analysis indicated that miR-182/miR-100 ratio was an independent prognostic factor for overall survival (Hazard ratio: 7.142; 95% CI: 2.106 - 9.891; P analysis revealed that high-level of miR-182/miR-100 ratio was significantly correlated with shortened survival time for BCa patients (P ratio may serve as a novel promising biomarker for diagnosis and survival prediction in BCa. Further studies are needed to elucidate the role of miR-182/miR-100 ratio as a non‑invasive diagnostic tool for BCa.

  4. MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2014-07-01

    Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

  5. 25 CFR 39.722 - What transportation information must day schools, on-reservation boarding schools and peripheral...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What transportation information must day schools, on-reservation boarding schools and peripheral dormitory schools report? 39.722 Section 39.722 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Student...

  6. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Søkilde, Rolf

    2014-01-01

    PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One...... of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target...... PTEN. METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry. RESULTS: miR-486-5p and miR-139-5p...

  7. Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation.

    Science.gov (United States)

    Revathidevi, Sundaramoorthy; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Rajkumar, Kottayasamy Seenivasagam; Ramani, Rajendran; Rajaraman, Ramamurthy; Ajay, Chandrasekar; Munirajan, Arasambattu Kannan

    2016-09-01

    Breast cancer and cervical cancer are the leading causes of death in women worldwide as well as in India, whilst oral cancer is the top most common cancer among Asian especially in Indian men in terms of both incidence and mortality rate. Genetic factors determining the predisposition to cancer are being explored to identify the signature genetic variations associated with these cancers. Recently, a germline deletion polymorphism in APOBEC3 gene cluster which completely deletes APOBEC3B coding region has been studied for its association with cancer risk. We screened the germline deletion polymorphism in 409 cancer patients (224 breast cancer, 88 cervical cancer and 97 oral cancer samples), 478 controls and 239 cervical cancer tissue DNAs of South Indian origin. The results suggest that the APOBEC3A/3B deletion polymorphism is not significantly associated with cancer risk in our study population (OR 0.739, 95 % CI, p value 0.91457). Considering the viral restriction property of APOBEC3s, we also screened cervical cancer tissue DNAs for the human papilloma virus infection. We observed a gradual increase in the frequency of HPV16 infection from AA/BB cases (66.86 %) to AA/-- cases (71.43) which signifies the impact of this deletion polymorphism in HPV infection. In addition, we performed in silico analysis to understand the effect of this polymorphism on miRNA regulation of the APOBEC3A/3B fusion transcript. Only 8 APOBEC3B targeting miRNAs were observed to regulate the fusion transcript of which miR-34b-3p and miR-138-5p were found to be frequently downregulated in cancers suggesting miRNA-mediated deregulation of APOBEC3A expression in cancer patients harbouring this particular deletion polymorphism.

  8. Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed miRNAs including miR-200c-3p as a prognostic marker

    International Nuclear Information System (INIS)

    Vilming Elgaaen, Bente; Olstad, Ole Kristoffer; Haug, Kari Bente Foss; Brusletto, Berit; Sandvik, Leiv; Staff, Anne Cathrine; Gautvik, Kaare M; Davidson, Ben

    2014-01-01

    Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these mi

  9. Implementing a reward and reminder underage drinking prevention program in convenience stores near Southern California American Indian reservations.

    Science.gov (United States)

    Moore, Roland S; Roberts, Jennifer; McGaffigan, Richard; Calac, Daniel; Grube, Joel W; Gilder, David A; Ehlers, Cindy L

    2012-09-01

    Underage drinking is associated with a number of social and public health consequences. Preventing access to alcohol is one approach to reducing underage drinking. This study assesses the efficacy of a culturally tailored "reward and reminder" program aimed at reducing convenience store alcohol sales to youth living on or near nine American Indian reservations. First, tribal council proclamations were sought to support underage drinking prevention, including reward and reminder efforts. Then, decoys (volunteers over 21 years of age but judged to look younger) attempted to purchase alcohol without identification. Clerks who asked for identification were given "rewards" (gift cards and congratulatory letters), whereas clerks who did not were given "reminders" of the law regarding sales to minors. Following an initial baseline of 12 purchase attempts, three repeated reward and reminder visits were made to 13 convenience stores selling alcohol within 10 miles of the reservations (n = 51 total attempts). Five of nine tribal councils passed resolutions in support of the program. The baseline sales rate without requesting ID was 33%. Similarly, 38% of stores in the first reward and reminder visit round failed to request identification. However, in the following two reward and reminder rounds, 0% of the stores failed to request identification. These results indicate that environmental community-level underage drinking prevention strategies to reduce alcohol sales near rural reservations are feasible and can be effective. Environmental prevention strategies within reservation communities support integrated supply and demand reduction models for reducing underage drinking.

  10. MiMiR: a comprehensive solution for storage, annotation and exchange of microarray data

    Directory of Open Access Journals (Sweden)

    Rahman Fatimah

    2005-11-01

    Full Text Available Abstract Background The generation of large amounts of microarray data presents challenges for data collection, annotation, exchange and analysis. Although there are now widely accepted formats, minimum standards for data content and ontologies for microarray data, only a few groups are using them together to build and populate large-scale databases. Structured environments for data management are crucial for making full use of these data. Description The MiMiR database provides a comprehensive infrastructure for microarray data annotation, storage and exchange and is based on the MAGE format. MiMiR is MIAME-supportive, customised for use with data generated on the Affymetrix platform and includes a tool for data annotation using ontologies. Detailed information on the experiment, methods, reagents and signal intensity data can be captured in a systematic format. Reports screens permit the user to query the database, to view annotation on individual experiments and provide summary statistics. MiMiR has tools for automatic upload of the data from the microarray scanner and export to databases using MAGE-ML. Conclusion MiMiR facilitates microarray data management, annotation and exchange, in line with international guidelines. The database is valuable for underpinning research activities and promotes a systematic approach to data handling. Copies of MiMiR are freely available to academic groups under licence.

  11. Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma.

    Science.gov (United States)

    Chuang, Tsai-Der; Khorram, Omid

    2016-01-01

    To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-κB, specific protein 1 (SP1), and DNA methylation in its regulation. Experimental study. Academic research laboratory. Women undergoing hysterectomy for leiomyoma. Over- and underexpression of miR-29c; blockade of transcription factors. MiR-29c and its target gene levels in leiomyoma and the effects of blockade of transcription factors on miR-29c expression. Leiomyoma as compared with myometrium expressed significantly lower levels of miR-29c, with an inverse relationship with expression of its targets, COL3A1 and DNMT3A. Gain of function of miR-29c inhibited the expression of COL3A1 and DNMT3A at protein and mRNA levels, secreted COL3A1, and rate of cell proliferation. Loss of function of miR-29c had the opposite effect. E2, P, and their combination inhibited miR-29c in leiomyoma smooth muscle cells (LSMC). Phosphorylated NF-κB (p65) and SP1 protein expression were significantly increased in leiomyoma. SiRNA knockdown of SP1 and DNMT3A or their specific inhibitors significantly increased the expression of miR-29c, accompanied by the inhibition of cellular and secreted COL3A1 in siRNA-treated cells. Knockdown of p65 also induced miR-29c expression but had no effect on COL3A1 expression. MiR-29c expression is suppressed in leiomyoma, resulting in an increase in expression of its targets COL3A1 and DNMT3A. The suppression of miR-29c in LSMC is primarily mediated by SP1, NF-κB signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, Declan J., E-mail: dj.mckenna@ulster.ac.uk [Biomedical Sciences Research Institute, University of Ulster, Coleraine, Co. Derry BT52 1SA (United Kingdom); Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom); Patel, Daksha, E-mail: d.patel@qub.ac.uk [Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom); McCance, Dennis J., E-mail: d.mccance@qub.ac.uk [Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom)

    2014-01-05

    A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR-24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16 (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during proliferation and differentiation of HFKs. We show that the induction of both miR-24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as miR-205 expression is dependent on pRb expression. Finally, we provide evidence that miR-24 effects in the cell may be due to targeting of cyclin dependent kinase inhibitor p27. In summary, these results indicate that expression of both miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one mechanism by which HPV onco-proteins can disrupt the balance between proliferation and differentiation in keratinocytes. - Highlights: • miR-24 and miR-205 are induced during keratinocyte differentiation. • This induction is lost in keratinocytes expressing HPV onco-proteins E6 and E7. • miR-205 is dependent upon pRb expression. • miR-24 targets p27 in cycling keratinocytes.

  13. miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes

    International Nuclear Information System (INIS)

    McKenna, Declan J.; Patel, Daksha; McCance, Dennis J.

    2014-01-01

    A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR-24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16 (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during proliferation and differentiation of HFKs. We show that the induction of both miR-24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as miR-205 expression is dependent on pRb expression. Finally, we provide evidence that miR-24 effects in the cell may be due to targeting of cyclin dependent kinase inhibitor p27. In summary, these results indicate that expression of both miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one mechanism by which HPV onco-proteins can disrupt the balance between proliferation and differentiation in keratinocytes. - Highlights: • miR-24 and miR-205 are induced during keratinocyte differentiation. • This induction is lost in keratinocytes expressing HPV onco-proteins E6 and E7. • miR-205 is dependent upon pRb expression. • miR-24 targets p27 in cycling keratinocytes

  14. miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132

    Science.gov (United States)

    Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

    2011-01-01

    When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804

  15. Geology and hydrology of the Fort Belknap Indian Reservation, Montana

    Science.gov (United States)

    Alverson, Douglas C.

    1965-01-01

    The Fort Belknap Indian Reservation includes an area of 970 square miles in north-central Montana. At its north edge is the Milk River valley, which is underlain by Recent alluvium of the Milk River, glacial deposits, and alluvial deposits of the preglacial Missouri River, which carved and occupied this valley before the Pleistocene Epoch. Rising gently to the south is an undulating glaciated plain broken only by three small syenite porphyry intrusions. Underlying the glacial till of the plain are Upper Cretaceous shale and sandstone of the Bearpaw and Judith River Formations. At the south end of the reservation, 40 miles from the Milk River, an intrusion of syenite porphyry in Tertiary time uplifted, tilted, and exposed the succession of sedimentary rocks overlying the Precambrian metamorphic basement. The sedimentary rocks include 1,000 feet of sandstone and shale of Cambrian age; 2,000 feet of limestone and dolomite of Ordovician, Devonian, and Mississippian age; 400 feet of shale and limestone of Jurassic age; and 3,500 feet of sandstone, siltstone, and shale of Cretaceous age. Extensive gravel terraces of Tertiary and Quaternary age bevel the upturned bedrock formations exposed around the Little Rocky Mountains. Ground water under water-table conditions is obtained at present from alluvium, glaciofluvial deposits, and the Judith River Formation. The water table ranges in depth from a few feet beneath the surface in the Milk River valley alluvium to more than 100 feet deep in the Judith River Formation. Yields to wells are generally low but adequate for domestic and stock-watering use. Quality of the water ranges from highly mineralized and unusable to excellent; many wells in the Milk River valley have been abandoned because of the alkalinity of their water. Potential sources of additional ground-water supplies are the alluvial gravel of creeks issuing from the Little Rocky Mountains and some extensive areas of terrace gravel. The uplift and tilting of the

  16. A retirement and a reservation: a retrospective autobiography.

    Science.gov (United States)

    Lee, Sok K

    2012-01-01

    A retirement is a rite of passage that requires careful planning, because it forces a retiree to make a shift in the paradigm in life. For 37 years, I was a healing professional, a breadwinner, and a working spouse. I am now a jobless loner, an inactive pensioner, and a homebound spouse. In this retrospective autobiography, I suggest a few points to help my younger colleagues to better their upcoming retirement: professional, financial, social, and familial. To overcome Erikson's identity crisis, I volunteered to be a wounded healer at Warm Springs Indian Reservation. My volunteer medical service at Warm Springs Indian Reservation was a good antidote to creatively overcome my postretirement blues.

  17. Social Network Analysis of the Caste-Based Reservation System in India

    OpenAIRE

    Iyengar, S. R. S.; Parasuram, Aishwarya; Saini, Jaspal Singh

    2015-01-01

    It has been argued that the reservation system in India, which has existed since the time of Indian Independence (1947), has caused more havoc and degradation than progress. This being a popular public opinion, these notions have not been based on any rigorous scientific study or research. In this paper, we revisit the cultural divide among the Indian population from a purely social networks based approach. We study the reservation system in detail, starting from its past and observing its ef...

  18. miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict

    2013-01-01

    were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out...... genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC. CONCLUSION: The present study provides the first evidence that miR-20b, miR-98, miR-125b-1*, and let-7e* are deregulated in patients with UC. The level...

  19. miRSponge: a manually curated database for experimentally supported miRNA sponges and ceRNAs.

    Science.gov (United States)

    Wang, Peng; Zhi, Hui; Zhang, Yunpeng; Liu, Yue; Zhang, Jizhou; Gao, Yue; Guo, Maoni; Ning, Shangwei; Li, Xia

    2015-01-01

    In this study, we describe miRSponge, a manually curated database, which aims at providing an experimentally supported resource for microRNA (miRNA) sponges. Recent evidence suggests that miRNAs are themselves regulated by competing endogenous RNAs (ceRNAs) or 'miRNA sponges' that contain miRNA binding sites. These competitive molecules can sequester miRNAs to prevent them interacting with their natural targets to play critical roles in various biological and pathological processes. It has become increasingly important to develop a high quality database to record and store ceRNA data to support future studies. To this end, we have established the experimentally supported miRSponge database that contains data on 599 miRNA-sponge interactions and 463 ceRNA relationships from 11 species following manual curating from nearly 1200 published articles. Database classes include endogenously generated molecules including coding genes, pseudogenes, long non-coding RNAs and circular RNAs, along with exogenously introduced molecules including viral RNAs and artificial engineered sponges. Approximately 70% of the interactions were identified experimentally in disease states. miRSponge provides a user-friendly interface for convenient browsing, retrieval and downloading of dataset. A submission page is also included to allow researchers to submit newly validated miRNA sponge data. Database URL: http://www.bio-bigdata.net/miRSponge. © The Author(s) 2015. Published by Oxford University Press.

  20. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    International Nuclear Information System (INIS)

    Park, Jong-Kook; Henry, Jon C.; Jiang, Jinmai; Esau, Christine; Gusev, Yuriy; Lerner, Megan R.; Postier, Russell G.; Brackett, Daniel J.; Schmittgen, Thomas D.

    2011-01-01

    Research highlights: → The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. → miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. → miR-132 and miR-212 expression is increased by a β2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G 2 /M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism.

  1. Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Naji, Mohammad; Nekoonam, Saeid; Aleyasin, Ashraf; Arefian, Ehsan; Mahdian, Reza; Azizi, Elham; Shabani Nashtaei, Maryam; Amidi, Fardin

    2018-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies that affects women in reproductive age. MicroRNAs (miRNAs) play crucial roles in normal function of female reproductive system and folliculogenesis. Deregulated expression of miRNAs in PCOS condition may be significantly implicated in the pathogenesis of PCOS. We determined relative expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells (GLCs), follicular fluid (FF), and serum of PCOS patients. Human subjects were divided into PCOS (n = 20) and control (n = 21) groups. GLCs, FF, and serum were isolated and stored. RNA isolation was performed and cDNA was reversely transcribed using specific stem-loop RT primers. Relative expression of miRNAs was calculated after normalization against U6 expression. Correlation of miRNAs' expression level with basic clinical features and predictive value of miRNAs in FF and serum were appraised. Relative expression of miR-145 and miR-182 in GLCs was significantly decreased in PCOS, but miR-182 in FF of PCOS patients revealed up-regulated levels. Significant correlations between level of miRNAs in FF and serum and hormonal profile of subjects were observed. MiR-182 in FF showed a significant predictive value with AUC of 0.73, 76.4% sensitivity, and 70.5% specificity which was improved after combination of miR-182 and miR-145. A significant dysregulation of miR-145 and miR-182 in GLCs of PCOS may indicate their involvement in pathogenesis of PCOS. Differential up-regulation of miR-182 in FF of PCOS patients with its promising predictive values for discrimination of PCOS reinforced the importance of studying miRNAs' profile in FF.

  2. Investigation of miRNA Biology by Bioinformatic Tools and Impact of miRNAs in Colorectal Cancer: Regulatory Relationship of c-Myc and p53 with miRNAs

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2007-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that mediate gene expression at the posttranscriptional and translational levels and have been demonstrated to be involved in diverse biological functions. Mounting evidence in recent years has shown that miRNAs play key roles in tumorigenesis due to abnormal expression of and mutations in miRNAs. High throughput miRNA expression profiling of several major tumor types has identified miRNAs associated with clinical diagnosis and prognosis of cancer treatment. Previously our group has discovered a novel regulatory relationship between tumor suppressor gene p53 with miRNAs expression and a number of miRNA promoters contain putative p53 binding sites. In addition, others have reported that c-myc can mediate a large number of miRNAs expression. In this review, we will emphasize algorithms to identify mRNA targets of miRNAs and the roles of miRNAs in colorectal cancer. In particular, we will discuss a novel regulatory relationship of miRNAs with tumor suppressor p53 and c-myc. miRNAs are becoming promising novel targets and biomarkers for future cancer therapeutic development and clinical molecular diagnosis.

  3. Indian Health Disparities

    Science.gov (United States)

    ... reservations and in rural communities, mostly in the western United States and Alaska. The American Indian and ... Office of Finance and Accounting - 10E54 Office of Human Resources - 11E53A Office of Information Technology - 07E57B Office of ...

  4. The miR-1000-p53 pathway regulates apoptosis and virus infection in shrimp.

    Science.gov (United States)

    Gong, Yi; Ju, Chenyu; Zhang, Xiaobo

    2015-10-01

    The p53 protein plays an important role in apoptosis which is involved in the immunity of animals. However, effects of the miRNA-mediated regulation of p53 expression on apoptosis and virus infection are not extensively investigated. To address this issue, the miRNA-mediated p53-dependent apoptotic pathway was explored in this study. The results indicated that p53 could regulate the apoptotic activity of Marsupenaeus japonicas shrimp and influence the infection of white spot syndrome virus (WSSV). The further data presented that miR-1000 could target the 3'-untranslated region (3'UTR) of p53 gene. The results of in vivo experiments showed that the miR-1000 overexpression led to significant decreases of shrimp apoptotic activity and the capacity of WSSV infection, while the miR-1000 silencing resulted in significant increases of apoptotic activity and virus infection, indicating that miR-1000 took great effects on apoptosis and virus infection by targeting p53. Therefore, our study revealed a novel mechanism that the miR-1000-p53 pathway regulated apoptosis and virus infection in shrimp. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 25 CFR 91.11 - Domestic animals in village reserves.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Domestic animals in village reserves. 91.11 Section 91.11... VILLAGES, OSAGE RESERVATION, OKLAHOMA § 91.11 Domestic animals in village reserves. (a) No livestock shall... owner of the animal, if known, by certified mail or by posting in the village square. The notice shall...

  6. Cointegrating MiDaS Regressions and a MiDaS Test

    OpenAIRE

    J. Isaac Miller

    2011-01-01

    This paper introduces cointegrating mixed data sampling (CoMiDaS) regressions, generalizing nonlinear MiDaS regressions in the extant literature. Under a linear mixed-frequency data-generating process, MiDaS regressions provide a parsimoniously parameterized nonlinear alternative when the linear forecasting model is over-parameterized and may be infeasible. In spite of potential correlation of the error term both serially and with the regressors, I find that nonlinear least squares consistent...

  7. "Seed-Milarity" confers to hsa-miR-210 and hsa-miR-147b similar functional activity.

    Directory of Open Access Journals (Sweden)

    Thomas Bertero

    Full Text Available Specificity of interaction between a microRNA (miRNA and its targets crucially depends on the seed region located in its 5'-end. It is often implicitly considered that two miRNAs sharing the same biological activity should display similarity beyond the strict six nucleotide region that forms the seed, in order to form specific complexes with the same mRNA targets. We have found that expression of hsa-miR-147b and hsa-miR-210, though triggered by different stimuli (i.e. lipopolysaccharides and hypoxia, respectively, induce very similar cellular effects in term of proliferation, migration and apoptosis. Hsa-miR-147b only shares a "minimal" 6-nucleotides seed sequence with hsa-miR-210, but is identical with hsa-miR-147a over 20 nucleotides, except for one base located in the seed region. Phenotypic changes induced after heterologous expression of miR-147a strikingly differ from those induced by miR-147b or miR-210. In particular, miR-147a behaves as a potent inhibitor of cell proliferation and migration. These data fit well with the gene expression profiles observed for miR-147b and miR-210, which are very similar, and the gene expression profile of miR-147a, which is distinct from the two others. Bioinformatics analysis of all human miRNA sequences indicates multiple cases of miRNAs from distinct families exhibiting the same kind of similarity that would need to be further characterized in terms of putative functional redundancy. Besides, it implies that functional impact of some miRNAs can be masked by robust expression of miRNAs belonging to distinct families.

  8. Identification, characterization and expression analysis of pigeonpea miRNAs in response to Fusarium wilt.

    Science.gov (United States)

    Hussain, Khalid; Mungikar, Kanak; Kulkarni, Abhijeet; Kamble, Avinash

    2018-05-05

    Upon confrontation with unfavourable conditions, plants invoke a very complex set of biochemical and physiological reactions and alter gene expression patterns to combat the situations. MicroRNAs (miRNAs), a class of small non-coding RNA, contribute extensively in regulation of gene expression through translation inhibition or degradation of their target mRNAs during such conditions. Therefore, identification of miRNAs and their targets holds importance in understanding the regulatory networks triggered during stress. Structure and sequence similarity based in silico prediction of miRNAs in Cajanus cajan L. (Pigeonpea) draft genome sequence has been carried out earlier. These annotations also appear in related GenBank genome sequence entries. However, there are no reports available on context dependent miRNA expression and their targets in pigeonpea. Therefore, in the present study we addressed these questions computationally, using pigeonpea EST sequence information. We identified five novel pigeonpea miRNA precursors, their mature forms and targets. Interestingly, only one of these miRNAs (miR169i-3p) was identified earlier in draft genome sequence. We then validated expression of these miRNAs, experimentally. It was also observed that these miRNAs show differential expression patterns in response to Fusarium inoculation indicating their biotic stress responsive nature. Overall these results will help towards better understanding the regulatory network of defense during pigeonpea -pathogen interactions and role of miRNAs in the process. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Analysis of miRNA expression profiles in melatonin-exposed GC-1 spg cell line.

    Science.gov (United States)

    Zhu, Xiaoling; Chen, Shuxiong; Jiang, Yanwen; Xu, Ying; Zhao, Yun; Chen, Lu; Li, Chunjin; Zhou, Xu

    2018-02-05

    Melatonin is an endocrine neurohormone secreted by pinealocytes in the pineal gland. It exerts diverse physiological effects, such as circadian rhythm regulator and antioxidant. However, the functional importance of melatonin in spermatogenesis regulation remains unclear. The objectives of this study are to: (1) detect melatonin affection on miRNA expression profiles in GC-1 spg cells by miRNA deep sequencing (DeepSeq) and (2) define melatonin affected miRNA-mRNA interactions and associated biological processes using bioinformatics analysis. GC-1 spg cells were cultured with melatonin (10 -7 M) for 24h. DeepSeq data were validated using quantitative real-time reverse transcription polymerase chain reaction analysis (qRT-PCR). A total of 176 miRNA expressions were found to be significantly different between two groups (fold change of >2 or melatonin could regulate the expression of miRNA to perform its physiological effects in GC-1 spg cells. These results should be useful to investigate the biological function of miRNAs regulated by melatonin in spermatogenesis and testicular germ cell tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 76 FR 2409 - Proclaiming Certain Lands, Lots 15 and 16 Acquisition, as an Addition to the Bay Mills Indian...

    Science.gov (United States)

    2011-01-13

    ... Acquisition, as an Addition to the Bay Mills Indian Reservation for the Bay Mills Indian Community of Michigan..., more or less, to be added to the Bay Mills Indian Reservation for the Bay Mills Indian Community of... the land described below. The land was proclaimed to be an addition to the Bay Mills Indian...

  11. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong-Kook [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Henry, Jon C. [Department of Surgery, Ohio State University, Columbus, OH 43210 (United States); Jiang, Jinmai [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Esau, Christine [Regulus Therapeutics, Carlsbad, CA (United States); Gusev, Yuriy [Lombardi Cancer Center, Georgetown University, Washington, DC (United States); Lerner, Megan R. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Postier, Russell G. [Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Brackett, Daniel J. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States)

    2011-03-25

    Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.

  12. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci.

    Directory of Open Access Journals (Sweden)

    Stefano Comazzetto

    2014-10-01

    Full Text Available Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449 that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility.

  13. miR-425 inhibits melanoma metastasis through repression of PI3K-Akt pathway by targeting IGF-1.

    Science.gov (United States)

    Liu, Pei; Hu, Yaotian; Ma, Ling; Du, Min; Xia, Lin; Hu, Zhensheng

    2015-10-01

    miR-425 is a potential tumor suppressor in cancer, but its role in melanoma is still unknown. We aim to investigate miR-425 expression in melanoma tissues and cell lines. Next, cell proliferation, cell cycle, apoptosis and metastasis will be studied using lentivirus-mediated gain-of-function studies. The predicted results are stable miR-425 inhibits cell proliferation and metastasis and induced cell apoptosis. It is predicted that IGF-1 is a potential target gene of miR-495 by bioinformatics analysis. Then luciferase assay analysis identifies IGF-1 as a new direct target gene of miR-425 and miR-425 inhibits melanoma cancer progression via IGF-1. Collectively, our findings suggested that miR-425 may function as a tumor suppressor in melanoma by targeting IGF-1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Agnelli Luca

    2008-08-01

    Full Text Available Abstract Background The role of microRNAs (miRNAs in multiple myeloma (MM has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs and focused on transcripts whose expression varied significantly across the dataset. Methods miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets. Results We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and

  15. MiR-422a targets MAPKK6 and regulates cell growth and apoptosis in colorectal cancer cells.

    Science.gov (United States)

    Li, Peng; Li, Qingmin; Zhang, Yanqiang; Sun, Shaojun; Liu, Shuntao; Lu, Zhaoxi

    2018-03-19

    The important role of miR-422a in tumor has been reported in several studies. Recent research discovered that the expression of miR-422a was significantly decreased in colorectal cancer tissues, providing miR-422a as a tumor suppressor in CRC. However, the concrete mechanism of miR-422a regulating CRC cell is still unclear. In this study, we demonstrated that miR-422a could inhibit CRC cell growth and promote cell apoptosis via in vitro analyses. Moreover, computational methods were adopted to identify the targets of miR-422a. We found MAPKK6 was the direct target of miR-422a. Consequently, we further elucidated that miR-422a inhibited CRC cell growth and induced cell apoptosis by inhibiting p38/MAPK pathway. Besides that, we established the tumor xenograft model using nude mice and the inhibitory effects on tumor volumes and weights by miR-422a mimic transfection were also detected. Taken together, these findings demonstrated miR-422a exerted anti-cancer activities on CRC, which could be potentially used for CRC prognosis prediction and treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Khalda S. Amr

    2017-12-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the common lethal types of tumor all over the world. The lethality of HCC accounts for many reasons. One of them, the lack of reliable diagnostic markers at the early stage, in this context, serum miRNAs became promising diagnostic biomarkers. Herein, we aimed to identify the predictive value of two miRNAs (miR-122 and miR-224 in plasma of patients with HCC preceded by chronic HCV infection. Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups; 40 patients with HCC related to HCV, 40 with CHC patients and 20 healthy volunteers. This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups (P 1.2 (RQ and (AUC = 0.93, P < 0.001, while the accuracy of AFP to diagnose HCC was (AUC: 0.619; P = 0.06. In conclusion, the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage.

  17. Bacillus subtilis affects miRNAs and flavanoids production in Agrobacterium-Tobacco interaction.

    Science.gov (United States)

    Nazari, Fahimeh; Safaie, Naser; Soltani, Bahram Mohammad; Shams-Bakhsh, Masoud; Sharifi, Mohsen

    2017-09-01

    Agrobacterium tumefaciens is a very destructive plant pathogen. Selection of effective biological agents against this pathogen depends on more insight into molecular plant defence responses during the biocontrol agent-pathogen interaction. Auxin as a phytohormone is a key contributor in pathogenesis and plant defence and accumulation of auxin transport carriers are accompanied by increasing in flavonoid and miRNAs concentrations during plant interactions with bacteria. The aim of this research was molecular analysis of Bacillus subtilis (ATCC21332) biocontrol effect against A. tumefaciens (IBRC-M10701) pathogen interacting with Nicotiana tabacum plants. Tobacco plants were either treated with both or one of the challenging bacteria and the expression of miRNAs inside the plants were analysed through qRT-PCR. The results indicated that the bacterial treatments affect expression level of nta-miRNAs. In tobacco plants treated only with A. tumefaciens the expression of nta-miR393 was more than that was recorded for nta-miR167 (3.8 folds, P subtilis (2.1 folds, P subtilis alone, was similar to the amount recorded for the plants challenged with the both bacteria. This study suggests a relationship between the upregulation of nta-miR167, nta-miR393 and accumulation of flavanoid compounds. Overall, the expression of these miRNAs as well as flavonoid derivatives has the potential of being used as biomarkers for the interaction of B. subtilis and A. tumefaciens model system in N. tabacum. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Yamashita, Ryo; Sato, Mitsuo; Kakumu, Tomohiko; Hase, Tetsunari; Yogo, Naoyuki; Maruyama, Eiichi; Sekido, Yoshitaka; Kondo, Masashi; Hasegawa, Yoshinori

    2015-01-01

    Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer cell lines, including H460, as well as one immortalized normal human bronchial epithelial cell line, HBEC4. miR-221 and miR-222 induced epithelial-to-mesenchymal transition (EMT)-like changes in a minority of HBEC4 cells but, unexpectedly, both the microRNAs rather suppressed their invasiveness. Consistent with the prior report, miR-221 and miR-222 promoted growth in H460; however, miR-221 suppressed growth in four other cell lines with no effects in one, and miR-222 suppressed growth in three cell lines but promoted growth in two. These are the first results to show tumor-suppressive effects of miR-221 and miR-222 in lung cancer cells, and we focused on clarifying the mechanisms. Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease

  19. Design of a Randomized Controlled Trial of a Web-Based Intervention to Reduce Cardiovascular Disease Risk Factors among Remote Reservation-Dwelling American Indian Adults with Type 2 Diabetes

    Science.gov (United States)

    Henderson, Jeffrey A.; Chubak, Jessica; O'Connell, Joan; Ramos, Maria C.; Jensen, Julie; Jobe, Jared B.

    2012-01-01

    We describe a randomized controlled trial, the Lakota Oyate Wicozani Pi Kte (LOWPK) trial, which was designed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease (CVD) among a group of remote reservation-dwelling adult American Indian men and women with type 2 diabetes…

  20. Altering β-cell number through stable alteration of miR-21 and miR-34a expression

    DEFF Research Database (Denmark)

    Backe, Marie Balslev; Novotny, Guy Wayne; Christensen, Dan Ploug

    2014-01-01

    RNAs, miR-21 and miR-34a, may be involved in mediating cytokine-induced β-cell dysfunction. Therefore, manipulation of miR-21 and miR-34a levels may potentially be beneficial to β cells. To study the effect of long-term alterations of miR-21 or miR-34a levels upon net β-cell number, we stably overexpressed...

  1. Data of expression status of miR- 29a and its putative target mitochondrial apoptosis regulatory gene DRP1 upon miR-15a and miR-214 inhibition

    Directory of Open Access Journals (Sweden)

    Muhammad Ishtiaq Jan

    2018-02-01

    Full Text Available Data is about the mitochondrial apoptosis regulatory framework genes PUMA, DRP1 (apoptotic, and ARC (anti-apoptotic analysis after the employment of their controlling miRNAs inhibitors. The data represents putative conserved targeting of seed regions of miR-15a, miR-29a, and miR-214 with respective target genes PUMA, DRP1, and ARC. Data is of cross interference in expression levels of one miRNA family, miR-29a and its putative target DRP1 upon the inhibitory treatment of other miRNAs 15a and 214. Keywords: DRP1, miR-15a, Apoptosis, miRNAs inhibition

  2. miR-7 Buffers Differentiation in the Developing Drosophila Visual System.

    Science.gov (United States)

    Caygill, Elizabeth E; Brand, Andrea H

    2017-08-08

    The 40,000 neurons of the medulla, the largest visual processing center of the Drosophila brain, derive from a sheet of neuroepithelial cells. During larval development, a wave of differentiation sweeps across the neuroepithelium, converting neuroepithelial cells into neuroblasts that sequentially express transcription factors specifying different neuronal cell fates. The switch from neuroepithelial cells to neuroblasts is controlled by a complex gene regulatory network and is marked by the expression of the proneural gene l'sc. We discovered that microRNA miR-7 is expressed at the transition between neuroepithelial cells and neuroblasts. We showed that miR-7 promotes neuroepithelial cell-to-neuroblast transition by targeting downstream Notch effectors to limit Notch signaling. miR-7 acts as a buffer to ensure that a precise and stereotypical pattern of transition is maintained, even under conditions of environmental stress, echoing the role that miR-7 plays in the eye imaginal disc. This common mechanism reflects the importance of robust visual system development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

    International Nuclear Information System (INIS)

    Torres, Anna; Torres, Kamil; Pesci, Anna; Ceccaroni, Marcello; Paszkowski, Tomasz; Cassandrini, Paola; Zamboni, Giuseppe; Maciejewski, Ryszard

    2012-01-01

    Alterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility. We investigated expression of mTOR kinase transcripts in 46 fresh tissue samples. Expression of miR-99a, miR-100 and miR-199b was investigated in the same group of fresh samples, and in additional 58 FFPE sections as well as in 48 plasma samples using qPCR. Relative quantification was performed using experimentally validated endogenous controls. mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. Down-regulation of the investigated miRNAs was discovered in plasma of EEC patients and miRNA signatures classified EEC tissues (miR-99a/miR-100/miR-199b) and plasma (miR-99a/miR-199b) samples with higher accuracy in comparison to single miRNAs. We also revealed that miR-100 was an independent prognostic marker of overall survival. We conclude that increased expression of mTOR kinase coexists with down-regulation of its targeting miRNAs, which could suggest a new mechanism of mTOR pathway alterations in EEC. In addition, our findings implicate that miRNA signatures can be considered promising biomarkers for early detection and prognosis of endometrioid endometrial carcinoma

  4. Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita.

    Science.gov (United States)

    Cui, Ruqiang; Zhang, Lei; Chen, Yuyan; Huang, Wenkun; Fan, Chengming; Wu, Qingsong; Peng, Deliang; da Silva, Washington; Sun, Xiaotang

    2017-05-01

    The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Copyright © 2017. Published by Elsevier Inc.

  5. Integrating miRNA and mRNA Expression Profiling Uncovers miRNAs Underlying Fat Deposition in Sheep

    Directory of Open Access Journals (Sweden)

    Guangxian Zhou

    2017-01-01

    Full Text Available MicroRNAs (miRNAs are endogenous, noncoding RNAs that regulate various biological processes including adipogenesis and fat metabolism. Here, we adopted a deep sequencing approach to determine the identity and abundance of miRNAs involved in fat deposition in adipose tissues from fat-tailed (Kazakhstan sheep, KS and thin-tailed (Tibetan sheep, TS sheep breeds. By comparing HiSeq data of these two breeds, 539 miRNAs were shared in both breeds, whereas 179 and 97 miRNAs were uniquely expressed in KS and TS, respectively. We also identified 35 miRNAs that are considered to be putative novel miRNAs. The integration of miRNA-mRNA analysis revealed that miRNA-associated targets were mainly involved in the gene ontology (GO biological processes concerning cellular process and metabolic process, and miRNAs play critical roles in fat deposition through their ability to regulate fundamental pathways. These pathways included the MAPK signaling pathway, FoxO and Wnt signaling pathway, and focal adhesion. Taken together, our results define miRNA expression signatures that may contribute to fat deposition and lipid metabolism in sheep.

  6. Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

    DEFF Research Database (Denmark)

    Welten, S. M. J.; Bastiaansen, Ajnm; de Jong, R. C. M.

    2014-01-01

    in mice after single femoral artery ligation. Methods and Results: Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4...... GSOs clearly improved blood flow recovery after ischemia. Mice treated with GSO-495 or GSO-329 showed increased perfusion already after 3 days (30% perfusion versus 15% in control), and those treated with GSO-329 showed a full recovery of perfusion after 7 days (versus 60% in control). Increased...

  7. A Canadian Indian Health Status Index.

    Science.gov (United States)

    Connop, P J

    1983-01-01

    Health care services for registered "band" Indians in Ontario are provided primarily by the Canadian Federal Government. Complex management methods preclude the direct involvement of Indian people in the decisions for their health resource allocation. Health indicators, need, and health status indexes are reviewed. The biostatistics of mortality and demography of the Indian and reference populations are aggregated with hospitalization/morbidity experience as the Chen G'1 Index, as an indicator of normative and comparative need. This is weighted by linear measurements of perceived need for preventive medicine programs, as ranked and scaled values of priorities, Zj. These were determined by community survey on 11 Indian reserves using a non-probabilistic psychometric method of "pair comparisons," based upon "Thurstone's Law of Comparative Judgement.," The calculation of the aggregate single unit Indian Health Status Index [Log.G'1].Zj and its potential application in a "zero-base" budget is described.

  8. Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

    Science.gov (United States)

    Matsuzaka, Yasunari; Kishi, Soichiro; Aoki, Yoshitsugu; Komaki, Hirofumi; Oya, Yasushi; Takeda, Shin-Ichi; Hashido, Kazuo

    2014-11-01

    Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as

  9. Identification of novel miRNAs and miRNA dependent developmental shifts of gene expression in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Shuhua Zhan

    Full Text Available microRNAs (miRNAs are small, endogenous RNAs of 20 approximately 25 nucleotides, processed from stem-loop regions of longer RNA precursors. Plant miRNAs act as negative regulators of target mRNAs predominately by slicing target transcripts, and a number of miRNAs play important roles in development. We analyzed a number of published datasets from Arabidopsis thaliana to characterize novel miRNAs, novel miRNA targets, and miRNA-regulated developmental changes in gene expression. These data include microarray profiling data and small RNA (sRNA deep sequencing data derived from miRNA biogenesis/transport mutants, microarray profiling data of mRNAs in a developmental series, and computational predictions of conserved genomic stem-loop structures. Our conservative analyses identified five novel mature miRNAs and seven miRNA targets, including one novel target gene. Two complementary miRNAs that target distinct mRNAs were encoded by one gene. We found that genes targeted by known miRNAs, and genes up-regulated or down-regulated in miRNA mutant inflorescences, are highly expressed in the wild type inflorescence. In addition, transcripts upregulated within the mutant inflorescences were abundant in wild type leaves and shoot meristems and low in pollen and seed. Downregulated transcripts were abundant in wild type pollen and seed and low in shoot meristems, roots and leaves. Thus, disrupting miRNA function causes the inflorescence transcriptome to resemble the leaf and meristem and to differ from pollen and seed. Applications of our computational approach to other species and the use of more liberal criteria than reported here will further expand the number of identified miRNAs and miRNA targets. Our findings suggest that miRNAs have a global role in promoting vegetative to reproductive transitions in A. thaliana.

  10. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

    Science.gov (United States)

    Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

    2013-11-01

    Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.

    Science.gov (United States)

    Mondal, Tanmoy; Lavanya, A V S; Mallick, Akash; Dadmala, Tulshiram L; Kumbhare, Ravindra M; Bhadra, Utpal; Bhadra, Manika Pal

    2017-06-01

    Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

  12. Genome wide predictions of miRNA regulation by transcription factors.

    Science.gov (United States)

    Ruffalo, Matthew; Bar-Joseph, Ziv

    2016-09-01

    Reconstructing regulatory networks from expression and interaction data is a major goal of systems biology. While much work has focused on trying to experimentally and computationally determine the set of transcription-factors (TFs) and microRNAs (miRNAs) that regulate genes in these networks, relatively little work has focused on inferring the regulation of miRNAs by TFs. Such regulation can play an important role in several biological processes including development and disease. The main challenge for predicting such interactions is the very small positive training set currently available. Another challenge is the fact that a large fraction of miRNAs are encoded within genes making it hard to determine the specific way in which they are regulated. To enable genome wide predictions of TF-miRNA interactions, we extended semi-supervised machine-learning approaches to integrate a large set of different types of data including sequence, expression, ChIP-seq and epigenetic data. As we show, the methods we develop achieve good performance on both a labeled test set, and when analyzing general co-expression networks. We next analyze mRNA and miRNA cancer expression data, demonstrating the advantage of using the predicted set of interactions for identifying more coherent and relevant modules, genes, and miRNAs. The complete set of predictions is available on the supporting website and can be used by any method that combines miRNAs, genes, and TFs. Code and full set of predictions are available from the supporting website: http://cs.cmu.edu/~mruffalo/tf-mirna/ zivbj@cs.cmu.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Identification and characterization of salt responsive miRNA-SSR markers in rice (Oryza sativa).

    Science.gov (United States)

    Mondal, Tapan Kumar; Ganie, Showkat Ahmad

    2014-02-10

    Salinity is an important abiotic stress that affects agricultural production and productivity. It is a complex trait that is regulated by different molecular mechanisms. miRNAs are non-coding RNAs which are highly conserved and regulate gene expression. Simple sequence repeats (SSRs) are robust molecular markers for studying genetic diversity. Although several SSR markers are available now, challenge remains to identify the trait-specific SSRs which can be used for marker assisted breeding. In order to understand the genetic diversity of salt responsive-miRNA genes in rice, SSR markers were mined from 130 members of salt-responsive miRNA genes of rice and validated among the contrasting panels of tolerant as well as susceptible rice genotypes, each with 12 genotypes. Although 12 miR-SSRs were found to be polymorphic, only miR172b-SSR was able to differentiate the tolerant and susceptible genotypes in 2 different groups. It had also been found that miRNA genes were more diverse in susceptible genotypes than the tolerant one (as indicated by polymorphic index content) which might interfere to form the stem-loop structure of premature miRNA and their subsequent synthesis in susceptible genotypes. Thus, we concluded that length variations of the repeats in salt responsive miRNA genes may be responsible for a possible sensitivity to salinity adaptation. This is the first report of characterization of trait specific miRNA derived SSRs in plants. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Conserved microRNA miR-8 in fat body regulates innate immune homeostasis in Drosophila.

    Science.gov (United States)

    Choi, In Kyou; Hyun, Seogang

    2012-05-01

    Antimicrobial peptides (AMPs) constitute a major arm of the innate immune system across diverse organisms. In Drosophila, septic injury by microbial pathogens rapidly induces the production of the AMPs in fat body via well elucidated pathways such as Toll and IMD. However, several epithelial tissues were reported to locally express AMPs without septic injury via poorly characterized ways. Here, we report that microRNA miR-8 regulates the levels of AMPs basally expressed in Drosophila. The levels of AMPs such as Drosomycin and Diptericin are significantly increased in miR-8 null animals in non-pathogen stimulated conditions. Analysis of various larval tissues revealed that the increase of Drosomycin is fat body specific. Supporting this observation, re-introduction of miR-8 only in the fat body restored the altered AMP expression in miR-8 null flies. Although loss of miR-8 impedes PI3K in the fat body, inhibition of PI3K does not phenocopy the AMP expression of miR-8 null flies, indicating that miR-8 regulates AMP independently of PI3K. Together, our findings suggest a role of miR-8 in systemic immune homeostasis in generally non-pathogenic conditions in flies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Turmeric (Curcuma longa): miRNAs and their regulating targets are involved in development and secondary metabolite pathways.

    Science.gov (United States)

    Singh, Noopur; Sharma, Ashok

    Turmeric has been used as a therapeutic herb over centuries in traditional medicinal systems due to the presence of several secondary metabolite compounds. microRNAs are known to regulate gene expression at the post-transcriptional level by transcriptional cleavage or translation repression. miRNAs have been demonstrated to play an active role in secondary metabolism regulation. The present work was focused on the identification of the miRNAs involved in the regulation of secondary metabolite and development process of turmeric. Eighteen miRNA families were identified for turmeric. Sixteen miRNA families were observed to regulate 238 target transcripts. LncRNAs targets of the putative miRNA candidates were also predicted. Our results indicated their role in binding, reproduction, stress, and other developmental processes. Gene annotation and pathway analysis illustrated the biological function of the targets regulated by the putative miRNAs. The miRNA-mediated gene regulatory network also revealed co-regulated targets that were regulated by two or more miRNA families. miR156 and miR5015 were observed to be involved in rhizome development. miR5021 showed regulation for terpenoid backbone biosynthesis and isoquinoline alkaloid biosynthesis pathways. The flavonoid biosynthesis pathway was observed to be regulated by miR2919. The analysis revealed the probable involvement of three miRNAs (miR1168.2, miR156b and miR1858) in curcumin biosynthesis. Other miRNAs were found to be involved in the growth and developmental process of turmeric. Phylogenetic analysis of selective miRNAs was also performed. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  16. Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus.

    Science.gov (United States)

    Risbud, Rashmi M; Lee, Carolyn; Porter, Brenda E

    2011-11-18

    Status epilepticus induces a cascade of protein expression changes contributing to the subsequent development of epilepsy. By identifying the cascade of molecular changes that contribute to the development of epilepsy we hope to be able to design therapeutics for preventing epilepsy. MicroRNAs influence gene expression by altering mRNA stability and/or translation and have been implicated in the pathology of multiple diseases. MiR21 and its co-transcript miR21, microRNAs produced from either the 5' or 3' ends of the same precursor RNA strand, are increased in the hippocampus following status epilepticus. We have identified a miR21 binding site, in the 3' UTR of neurotrophin-3 that inhibits translation. Neurotrophin-3 mRNA levels decrease in the hippocampus following SE concurrent with the increase in miR21. MiR21 levels in cultured hippocampal neurons inversely correlate with neurotrophin-3 mRNA levels. Treatment of hippocampal neuronal cultures with excess K(+)Cl(-), a depolarizing agent mimicking the episode of status epilepticus, also results in an increase in miR21 and a decrease in neurotrophin-3 mRNA. MiR21 is a candidate for regulating neurotrophin-3 signaling in the hippocampus following status epilepticus. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. miR-101 suppresses HBV replication and expression by targeting FOXO1 in hepatoma carcinoma cell lines.

    Science.gov (United States)

    Wang, Yanjing; Tian, Hui

    2017-05-20

    microRNAs (miRNAs) have been identified to participate in the progression of cancers and in the infection of viruses. miR-101 expression has been found to be suppressed by HBV, however, the regulatory relationship between miR-101 and HBV replication remains elusive. In this report, miR-101 was significantly downregulated in HepG2.2.15 cells with HBV expression. miR-101 overexpression dramatically suppressed HBV replication and expression. Oppositely, overexpression of FOXO1 significantly promoted HBV replication and expression. Moreover, luciferase reporter analysis, qRT-PCR analysis and western blot assay confirmed that FOXO1 was a functional target of miR-101. Furthermore, restored FOXO1 expression abolished the inhibitory effect of miR-101 overexpression on HBV replication and expression in HepG2.2.15 cells. Our data suggested that miR-101 suppressed HBV replication and expression partially by targeting FOXO1, providing new insights into the molecular mechanisms of miR-101 in HBV-host interactions and a promising therapeutic target for HBV replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Title IV Indian Education Program Evaluation, 1985-86.

    Science.gov (United States)

    Albuquerque Public Schools, NM. Planning, Research and Accountability.

    Public schools in Albuquerque, New Mexico, used a Title IV Part A grant to assist American Indian elementary and secondary school students in receiving passing grades and improving school-related behaviors. Canoncito Navajo Reservation, the Isleta Pueblo, and urban Indian students in Albuquerque participated in the program. Personnel consisted of…

  19. Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.

    Science.gov (United States)

    Maged, Ahmed M; Deeb, Wesam S; El Amir, Azza; Zaki, Sherif S; El Sawah, Heba; Al Mohamady, Maged; Metwally, Ahmed A; Katta, Maha A

    2018-04-01

    To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis. During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction. The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (Pendometriosis. Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis of endometriosis. © 2017 International Federation of Gynecology and Obstetrics.

  20. Asthma triggers on the Cheyenne River Indian Reservation in western South Dakota: the Breathing Relief Education and Tribal Health Empowerment (BREATHE) Study.

    Science.gov (United States)

    O'Leary, Rae; Wallace, James

    2012-02-01

    The purpose of this article is to better understand asthma triggers and possible causes of exacerbations among BREATHE participants on the Cheyenne River Indian Reservation in western South Dakota. To qualify for enrollment, participants had to have physician-diagnosed asthma, be uncontrolled and have persistent symptoms. Participants were asked to identify their top two asthma triggers throughout their one-year enrollment during initial visits and subsequent phone follow-ups. In addition, participant's medical records were reviewed for visits to the emergency department (ED) to demonstrate asthma exacerbations. In 2008, 127 interviews were conducted with 45 enrolled participants for a total of 254 results. Overall, the three most common self reported triggers were cold air, dust and smoke and these comprised nearly half (48.4 percent) of all reports. Dust was reported in 16.5 percent of interviews and ranked among the top four for every season. Smoke (12.6 percent) and cold air (19.3 percent) were leaders in all seasons except summer, but humid air, pollens and strong odors were unique to summer. Exercise/activity ranked high during the winter and spring, but was reported less in summer and fall. There was no identifiable trend in ER visits by season. People with asthma living on the Cheyenne River Indian Reservation or other locations with similar community and geographic demographics are most likely to suffer an asthma exacerbation from exposure to cold air, dust, smoke and exercise/activity. Asthma education is necessary on all levels, but information on avoidance and control of these most common reported triggers is especially important.

  1. Cortical Morphogenesis during Embryonic Development Is Regulated by miR-34c and miR-204

    DEFF Research Database (Denmark)

    Veno, Morten T.; Veno, Susanne T.; Rehberg, Kati

    2017-01-01

    The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across...

  2. Introduction of hsa-miR-103a and hsa-miR-1827 and hsa-miR-137 as new regulators of Wnt signaling pathway and their relation to colorectal carcinoma.

    Science.gov (United States)

    Fasihi, Ali; M Soltani, Bahram; Atashi, Amir; Nasiri, Shirzad

    2018-07-01

    Wnt signaling is hyper-activated in most of human cancers including colorectal carcinoma (CRC). Therefore, the introduction of new regulators for Wnt pathway possesses promising diagnostic and therapeutic applications in cancer medicine. Bioinformatics analysis introduced hsa-miR-103a, hsa-miR-1827, and hsa-miR-137 as potential regulators of Wnt signaling pathway. Here, we intended to examine the effect of these human miRNAs on Wnt signaling pathway components, on the cell cycle progression in CRC originated cell lines and their expression in CRC tissues. RT-qPCR results indicated upregulation of hsa-miR-103a, hsa-miR-1827, and downregulation of hsa-miR-137 in CRC tissues. Overexpression of hsa-miR-103a and hsa-miR-1827 in SW480 cells resulted in elevated Wnt activity, detected by both Top/Flash assay and RT-qPCR analysis. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules suggested that these miRNAs exerts their effect at the β-catenin degradation complex level. Then, RT-qPCR, dual luciferase assay, and western blotting analysis indicated that APC and APC2 transcripts were targeted by hsa-miR-103a, hsa-miR-1827 while, Wnt3a and β-catenin genes were upregulated. However, hsa-miR-137 downregulated Wnt3a and β-catenin genes. Further, hsa-miR-103a and hsa-miR-1827 overexpression resulted in cell cycle progression and reduced apoptotic rate in SW480 cells, unlike hsa-miR-137 overexpression which resulted in cell cycle suppression, detected by flowcytometry and Anexin analysis. Overall, our data introduced hsa-miR-103a, hsa-miR-1827 as onco-miRNAs and hsa-miR-137 as tumor suppressor which exert their effect through regulation of Wnt signaling pathway in CRC and introduced them as potential target for therapy. © 2017 Wiley Periodicals, Inc.

  3. CID-miRNA: A web server for prediction of novel miRNA precursors in human genome

    International Nuclear Information System (INIS)

    Tyagi, Sonika; Vaz, Candida; Gupta, Vipin; Bhatia, Rohit; Maheshwari, Sachin; Srinivasan, Ashwin; Bhattacharya, Alok

    2008-01-01

    microRNAs (miRNA) are a class of non-protein coding functional RNAs that are thought to regulate expression of target genes by direct interaction with mRNAs. miRNAs have been identified through both experimental and computational methods in a variety of eukaryotic organisms. Though these approaches have been partially successful, there is a need to develop more tools for detection of these RNAs as they are also thought to be present in abundance in many genomes. In this report we describe a tool and a web server, named CID-miRNA, for identification of miRNA precursors in a given DNA sequence, utilising secondary structure-based filtering systems and an algorithm based on stochastic context free grammar trained on human miRNAs. CID-miRNA analyses a given sequence using a web interface, for presence of putative miRNA precursors and the generated output lists all the potential regions that can form miRNA-like structures. It can also scan large genomic sequences for the presence of potential miRNA precursors in its stand-alone form. The web server can be accessed at (http://mirna.jnu.ac.in/cidmirna/)

  4. miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

    Science.gov (United States)

    Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

    2018-05-02

    ■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Mycobacterium tuberculosis decreases human macrophage IFN-γ responsiveness through miR-132 and miR-26a.

    Science.gov (United States)

    Ni, Bin; Rajaram, Murugesan V S; Lafuse, William P; Landes, Michelle B; Schlesinger, Larry S

    2014-11-01

    IFN-γ-activated macrophages play an essential role in controlling intracellular pathogens; however, macrophages also serve as the cellular home for the intracellular pathogen Mycobacterium tuberculosis. Based on previous evidence that M. tuberculosis can modulate host microRNA (miRNA) expression, we examined the miRNA expression profile of M. tuberculosis-infected primary human macrophages. We identified 31 differentially expressed miRNAs in primary human macrophages during M. tuberculosis infection by NanoString and confirmed our findings by quantitative real-time RT-PCR. In addition, we determined a role for two miRNAs upregulated upon M. tuberculosis infection, miR-132 and miR-26a, as negative regulators of transcriptional coactivator p300, a component of the IFN-γ signaling cascade. Knockdown expression of miR-132 and miR-26a increased p300 protein levels and improved transcriptional, translational, and functional responses to IFN-γ in human macrophages. Collectively, these data validate p300 as a target of miR-132 and miR-26a, and demonstrate a mechanism by which M. tuberculosis can limit macrophage responses to IFN-γ by altering host miRNA expression. Copyright © 2014 by The American Association of Immunologists, Inc.

  6. Distribution and source of barium in ground water at Cattaraugus Indian Reservation, southwestern New York

    Science.gov (United States)

    Moore, R.B.; Staubitz, W.W.

    1984-01-01

    High concentrations of dissolved barium have been found in ground water from bedrock wells on the Seneca Nation of Indians Reservation on Cattaraugus Creek in southwestern New York. Concentrations in 1982 were as high as 23.0 milligrams per liter , the highest found reported from any natural ground-water system in the world. The highest concentrations are in a bedrock aquifer and in small lenses of saturated gravel between bedrock and the overlying till. The bedrock aquifer is partly confined by silt, clay, and till. The high barium concentrations are attributed to dissolution of the mineral barite (BaSO4), which is present in the bedrock and possibly in overlying silt, clay, or till. The dissolution of barite seems to be controlled by action of sulfate-reducing bacteria, which alter the BaSO4 equilibrium by removing sulfate ions and permitting additional barite to dissolve. Ground water from the surficial, unconsolidated deposits and surface water in streams contain little or no barium. Because barium is chemically similar to calcium, it probably could be removed by cation exchange or treatments similar to those used for water softening. (USGS)

  7. Association of miR-548c-5p, miR-7-5p, miR-210-3p, miR-128-3p with recurrence in systemically untreated breast cancer

    DEFF Research Database (Denmark)

    Block, Ines; Burton, Mark; Sørensen, Kristina Pilekær

    2018-01-01

    . To validate their prognostic potential, we analyzed microRNA expression in an independent cohort (n = 110) using a pairmatched study design minimizing dependence of classical markers. The expression of hsa-miR-548c-5p was significantly associated with abridged disease-free survival (hazard ratio [HR]:1.96, p...... = 0.027). Contradicting published results, high hsa-miR516-3p expression was associated with favorable outcome (HR:0.29, p = 0.0068). The association is probably time-dependent indicating later relapse. Additionally, re-analysis of previously published expression data of two matching cohorts (n = 100......, n = 255) supports an association of hsa-miR-128-3p with shortened diseasefree survival (HR:2.48, p = 0.0033) and an upregulation of miR-7-5p (p = 0.0038; p = 0.039) and miR-210-3p (p = 0.031) in primary tumors of patients who experienced metastases. Further analysis may verify the prognostic...

  8. MiR-29c regulates the expression of miR-34c and miR-449a by targeting DNA methyltransferase 3a and 3b in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Niu, Man; Gao, Dan; Wen, Qiuyuan; Wei, Pingpin; Pan, Suming; Shuai, Cijun; Ma, Huiling; Xiang, Juanjuan; Li, Zheng; Fan, Songqing; Li, Guiyuan; Peng, Shuping

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is prevalent in South East Asia and Southern China particularly, despite the reported 5-year survival ratio is relative higher than other deadly cancers such as liver, renal, pancreas cancer, the lethality is characterized by high metastatic potential in the early stage and high recurrence rate after radiation treatment. MicroRNA-29c was found to be down-regulated in the serum as well as in the tissue of nasopharyngeal carcinoma tissue. In this study, we found accidentally that the transfection of pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a but doesn’t affect that of miR-222 using real-time quantitative PCR in nasopharyngeal carcinoma cell lines. To explore the molecular mechanism of the regulatory role, the cells are treated with 5-Aza-2-deoxycytidine (5-Aza-CdR) treatment and the level of miR-34c and miR-449a but not miR-222 accumulated by the treatment. DNA methyltransferase 3a, 3b were down-regulated by the 5-Aza-CdR treatment with western blot and real-time quantitative PCR. We found that pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a. We further found DNA methyltransferase 3a and 3b are the target gene of miR-29c. Restoration of miR-29c in NPC cells down-regulated DNA methyltransferase 3a, 3b, but not DNA methyltransferase T1. The regulation of miR-29c/DNMTs/miR-34c/449a is an important molecular axis of NPC development and targeting DNMTs or restoring of miR-29c might be a promising therapy strategy for the prevention of NPC

  9. Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD.

    Science.gov (United States)

    Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

    2015-01-28

    Although Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are ubiquitously expressed in EBV-associated tumors, the role of most BART miRNAs is unclear. In this study, we showed that Bcl-2-associated death promoter (BAD) expression was significantly lower in EBV-infected AGS-EBV cells than in EBV-negative AGS cells and investigated whether BART miRNAs target BAD. Using bioinformatics analysis, five BART miRNAs showing seed match with the 3' untranslated region (3'-UTR) of BAD were selected. Of these, only miR-BART20-5p reduced BAD expression when individually transfected into AGS cells. A luciferase assay revealed that miR-BART20-5p directly targets BAD. The expression of BAD mRNA and protein was decreased by miR-BART20-5p and increased by an inhibitor of miR-BART20-5p. PE-Annexin V staining and cell proliferation assays showed that miR-BART20-5p reduced apoptosis and enhanced cell growth. Furthermore, miR-BART20-5p increased chemoresistance to 5-fluorouracil and docetaxel. Our data suggest that miR-BART20-5p contributes to tumorigenesis of EBV-associated gastric carcinoma by directly targeting the 3'-UTR of BAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

    Science.gov (United States)

    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1.

    Science.gov (United States)

    Wang, Yunxia; Zhu, Kongxi; Yu, Weihua; Wang, Hongjuan; Liu, Lan; Wu, Qiong; Li, Shuai; Guo, Jianqiang

    2017-11-04

    Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3'-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3'-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo. And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 25 CFR 226.12 - Government reserves right to purchase oil.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Government reserves right to purchase oil. 226.12 Section... reserves right to purchase oil. Any of the executive departments of the U.S. Government shall have the... price as defined in § 226.11. ...

  13. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

  14. Normalization matters: tracking the best strategy for sperm miRNA quantification.

    Science.gov (United States)

    Corral-Vazquez, Celia; Blanco, Joan; Salas-Huetos, Albert; Vidal, Francesca; Anton, Ester

    2017-01-01

    biological processes. Hsa-miR-146b-5p and hsa-miR-92a-3p were more uniformly expressed than RNU6B, but their results still showed scant proximity to the reference method. The highest resemblance to MCR was achieved by hsa-miR-100-5p and hsa-miR-30a-5p. Normalization against the combination of both miRNAs reached the best proximity rank regarding the detected DE-miRNAs (Area Under the Curve = 0.8). This combination also exhibited the best performance in terms of the target genes predicted (72.3% of True Positives) and their corresponding enriched biological processes (70.4% of True Positives). Not applicable. This study is focused on sperm miRNA qRT-PCR analysis. The use of the selected normalizers in other cell types or tissues would still require confirmation. The search for new fertility biomarkers based on sperm miRNA expression using high-throughput assays is one of the upcoming challenges in the field of reproductive genetics. In this context, validation of the results using singleplex assays would be mandatory. The normalizer strategy suggested in this study would provide a universal option in this area, allowing for normalization of the validated data without causing meaningful variations of the results. Instead, qRT-PCR data normalization by RNU6B should be discarded in sperm-miRNA expression studies. This work was supported by the 2014/SGR00524 project (Agència de Gestió d'Ajuts Universitaris i de Recerca, Generalitat de Catalunya, Spain) and UAB CF-180034 grant (Universitat Autònoma de Barcelona). Celia Corral-Vazquez is a recipient of a Personal Investigador en Formació grant UAB/PIF2015 (Universitat Autònoma de Barcelona). The authors report no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Characterization of novel precursor miRNAs using next generation sequencing and prediction of miRNA targets in Atlantic halibut.

    Directory of Open Access Journals (Sweden)

    Teshome Tilahun Bizuayehu

    Full Text Available BACKGROUND: microRNAs (miRNAs are implicated in regulation of many cellular processes. miRNAs are processed to their mature functional form in a step-wise manner by multiple proteins and cofactors in the nucleus and cytoplasm. Many miRNAs are conserved across vertebrates. Mature miRNAs have recently been characterized in Atlantic halibut (Hippoglossus hippoglossus L.. The aim of this study was to identify and characterize precursor miRNA (pre-miRNAs and miRNA targets in this non-model flatfish. Discovery of miRNA precursor forms and targets in non-model organisms is difficult because of limited source information available. Therefore, we have developed a methodology to overcome this limitation. METHODS: Genomic DNA and small transcriptome of Atlantic halibut were sequenced using Roche 454 pyrosequencing and SOLiD next generation sequencing (NGS, respectively. Identified pre- miRNAs were further validated with reverse-transcription PCR. miRNA targets were identified using miRanda and RNAhybrid target prediction tools using sequences from public databases. Some of miRNA targets were also identified using RACE-PCR. miRNA binding sites were validated with luciferase assay using the RTS34st cell line. RESULTS: We obtained more than 1.3 M and 92 M sequence reads from 454 genomic DNA sequencing and SOLiD small RNA sequencing, respectively. We identified 34 known and 9 novel pre-miRNAs. We predicted a number of miRNA target genes involved in various biological pathways. miR-24 binding to kisspeptin 1 receptor-2 (kiss1-r2 was confirmed using luciferase assay. CONCLUSION: This study demonstrates that identification of conserved and novel pre-miRNAs in a non-model vertebrate lacking substantial genomic resources can be performed by combining different next generation sequencing technologies. Our results indicate a wide conservation of miRNA precursors and involvement of miRNA in multiple regulatory pathways, and provide resources for further research on mi

  16. 78 FR 14820 - Proclaiming Certain Lands as Reservation for the Tohono O'odham Nation of Arizona

    Science.gov (United States)

    2013-03-07

    ... the Tohono O'odham Nation of Arizona AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of... Affairs proclaimed approximately 642.27 acres, more or less, as the Tohono O'odham Nation Indian Reservation for the Tohono O'odham Nation Tribe of Indians of Arizona on February 28, 2013. DATE: The...

  17. 77 FR 1642 - Food Distribution Program on Indian Reservations: Income Deductions and Resource Eligibility

    Science.gov (United States)

    2012-01-11

    ..., Grant programs, Social programs, Indians, Reporting and recordkeeping requirements, Surplus agricultural... retroactive Social Security payments. The amendment would remove the language that provides these payments are... beneficiary is disabled; (e) Medicare premiums related to coverage under Title XVIII of the Social Security...

  18. Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma.

    Science.gov (United States)

    Truini, Anna; Coco, Simona; Nadal, Ernest; Genova, Carlo; Mora, Marco; Dal Bello, Maria Giovanna; Vanni, Irene; Alama, Angela; Rijavec, Erika; Biello, Federica; Barletta, Giulia; Merlo, Domenico Franco; Valentino, Alessandro; Ferro, Paola; Ravetti, Gian Luigi; Stigliani, Sara; Vigani, Antonella; Fedeli, Franco; Beer, David G; Roncella, Silvio; Grossi, Francesco

    2017-09-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date no molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed using biopsies on 27 unresected MPM patients with distinct clinical outcome: 15 patients had short survival (OS36 months). Three prognostic miRNAs (mir-99a, let-7c, and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High-risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high-risk score was independently associated with shorter OS (HR=3.14; 95% CI, 1.18-8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

  19. miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling.

    Science.gov (United States)

    Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O; You, Min

    2015-05-01

    Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and in primary Kupffer cells. In macrophages, ethanol substantially exacerbated LPS-mediated induction of miR-217 and production of proinflammatory cytokines compared with LPS or ethanol alone. Consistently, ethanol administration to mice led to increases in miR-217 abundance and increased production of inflammatory cytokines in isolated primary Kupffer cells exposed to the combination of ethanol and LPS. miR-217 promoted combined ethanol and LPS-mediated inhibition of sirtuin 1 expression and activity in macrophages. Moreover, miR-217-mediated sirtuin 1 inhibition was accompanied by increased activities of two vital inflammatory regulators, NF-κB and the nuclear factor of activated T cells c4. Finally, adenovirus-mediated overexpression of miR-217 led to steatosis and inflammation in mice. These findings suggest that miR-217 is a pivotal regulator involved in ethanol-induced hepatic inflammation. Strategies to inhibit hepatic miR-217 could be a viable approach in attenuating alcoholic hepatitis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Circulating microRNA (miRNA Expression Profiling in Plasma of Patients with Gestational Diabetes Mellitus Reveals Upregulation of miRNA miR-330-3p

    Directory of Open Access Journals (Sweden)

    Guido Sebastiani

    2017-12-01

    Full Text Available Gestational diabetes mellitus (GDM is characterized by insulin resistance accompanied by low/absent beta-cell compensatory adaptation to the increased insulin demand. Although the molecular mechanisms and factors acting on beta-cell compensatory response during pregnancy have been partially elucidated and reported, those inducing an impaired beta-cell compensation and function, thus evolving in GDM, have yet to be fully addressed. MicroRNAs (miRNAs are a class of small endogenous non-coding RNAs, which negatively modulate gene expression through their sequence-specific binding to 3′UTR of mRNA target. They have been described as potent modulators of cell survival and proliferation and, furthermore, as orchestrating molecules of beta-cell compensatory response and function in diabetes. Moreover, it has been reported that miRNAs can be actively secreted by cells and found in many biological fluids (e.g., serum/plasma, thus representing both optimal candidate disease biomarkers and mediators of tissues crosstalk(s. Here, we analyzed the expression profiles of circulating miRNAs in plasma samples obtained from n = 21 GDM patients and from n = 10 non-diabetic control pregnant women (24–33 weeks of gestation using TaqMan array microfluidics cards followed by RT-real-time PCR single assay validation. The results highlighted the upregulation of miR-330-3p in plasma of GDM vs non-diabetics. Furthermore, the analysis of miR-330-3p expression levels revealed a bimodally distributed GDM patients group characterized by high or low circulating miR-330 expression and identified as GDM-miR-330high and GDM-miR-330low. Interestingly, GDM-miR-330high subgroup retained lower levels of insulinemia, inversely correlated to miR-330-3p expression levels, and a significant higher rate of primary cesarean sections. Finally, miR-330-3p target genes analysis revealed major modulators of beta-cell proliferation and of insulin secretion, such as the

  1. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties...... of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge...... communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...

  2. miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice.

    Science.gov (United States)

    Zeng, Ping; Han, Wanhong; Li, Changyin; Li, Hu; Zhu, Dahai; Zhang, Yong; Liu, Xiaohong

    2016-09-01

    Skeletal muscle mass and homeostasis during postnatal muscle development and regeneration largely depend on adult muscle stem cells (satellite cells). We recently showed that global overexpression of miR-378 significantly reduced skeletal muscle mass in mice. In the current study, we used miR-378 transgenic (Tg) mice to assess the in vivo functional effects of miR-378 on skeletal muscle growth and regeneration. Cross-sectional analysis of skeletal muscle tissues showed that the number and size of myofibers were significantly lower in miR-378 Tg mice than in wild-type mice. Attenuated cardiotoxin-induced muscle regeneration in miR-378 Tg mice was found to be associated with delayed satellite cell activation and differentiation. Mechanistically, miR-378 was found to directly target Igf1r in muscle cells both in vitro and in vivo These miR-378 Tg mice may provide a model for investigating the physiological and pathological roles of skeletal muscle in muscle-associated diseases in humans, particularly in sarcopenia. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Web-based NGS data analysis using miRMaster: a large-scale meta-analysis of human miRNAs.

    Science.gov (United States)

    Fehlmann, Tobias; Backes, Christina; Kahraman, Mustafa; Haas, Jan; Ludwig, Nicole; Posch, Andreas E; Würstle, Maximilian L; Hübenthal, Matthias; Franke, Andre; Meder, Benjamin; Meese, Eckart; Keller, Andreas

    2017-09-06

    The analysis of small RNA NGS data together with the discovery of new small RNAs is among the foremost challenges in life science. For the analysis of raw high-throughput sequencing data we implemented the fast, accurate and comprehensive web-based tool miRMaster. Our toolbox provides a wide range of modules for quantification of miRNAs and other non-coding RNAs, discovering new miRNAs, isomiRs, mutations, exogenous RNAs and motifs. Use-cases comprising hundreds of samples are processed in less than 5 h with an accuracy of 99.4%. An integrative analysis of small RNAs from 1836 data sets (20 billion reads) indicated that context-specific miRNAs (e.g. miRNAs present only in one or few different tissues / cell types) still remain to be discovered while broadly expressed miRNAs appear to be largely known. In total, our analysis of known and novel miRNAs indicated nearly 22 000 candidates of precursors with one or two mature forms. Based on these, we designed a custom microarray comprising 11 872 potential mature miRNAs to assess the quality of our prediction. MiRMaster is a convenient-to-use tool for the comprehensive and fast analysis of miRNA NGS data. In addition, our predicted miRNA candidates provided as custom array will allow researchers to perform in depth validation of candidates interesting to them. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. 25 CFR 37.130 - Who establishes boundaries for Off-Reservation Boarding Schools?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Who establishes boundaries for Off-Reservation Boarding... GEOGRAPHIC BOUNDARIES Off-Reservation Boarding Schools § 37.130 Who establishes boundaries for Off-Reservation Boarding Schools? The Secretary or the Secretary's designee, in consultation with the affected...

  5. 25 CFR 141.58 - Records, reports, and obligations of reservation business owners.

    Science.gov (United States)

    2010-04-01

    ... shall keep records in accordance with generally accepted accounting principles. (b) Each reservation... 25 Indians 1 2010-04-01 2010-04-01 false Records, reports, and obligations of reservation business... ACTIVITIES BUSINESS PRACTICES ON THE NAVAJO, HOPI AND ZUNI RESERVATIONS Enforcement Powers, Procedures and...

  6. Common miR-590 Variant rs6971711 Present Only in African Americans Reduces miR-590 Biogenesis.

    Directory of Open Access Journals (Sweden)

    Xiaoping Lin

    Full Text Available MicroRNAs (miRNAs are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM. To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients. We identified a single nucleotide polymorphism (rs6971711, C57T SNP at the 17th position of mature miR-590-3p (= 57th position of pre-miR-590 that is common in individuals of African ancestry. SNP frequency was higher in African American HCM patients (n = 55 than ethnically-matched controls (n = 100, but the difference was not statistically significant (8.2% vs. 6.5%; p = 0.5. Using a cell culture system, we discovered that presence of this SNP resulted in markedly lower levels of mature miR-590-5p (39 ± 16%, p<0.003 and miR-590-3p (20 ± 2%, p<0.003, when compared with wild-type (WT miR-590, without affecting levels of pri-miR-590 and pre-miR-590. Consistent with this finding, the SNP resulted in reduced target suppression when compared to WT miR-590 (71% suppression by WT vs 60% suppression by SNP, p<0.03. Since miR-590 can regulate TGF-β, Activin A and Akt signaling, SNP-induced reduction in miR-590 biogenesis could influence cardiac phenotype by de-repression of these signaling pathways. Since the SNP is only present in African Americans, population studies in this patient population would be valuable to investigate effects of this SNP on myocyte function and cardiac physiology.

  7. Measurement of the forward-backward asymmetry in top quark-antiquark production in <mi>p><mi>p>¯ collisions using the <mi>lepton>+<mi>jets> channel

    Energy Technology Data Exchange (ETDEWEB)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Borysova, M.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M. -C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Falkowski, A.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Gogota, O.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orbaker, D.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M. -A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Savitskyi, M.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yin, H.; Yip, K.; Youn, S. W.; Yu, J. M.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.

    2014-10-01

    We present a measurement of the forward–backward asymmetry in top quark–antiquark production using the full Tevatron Run II data set collected by the D0 experiment at Fermilab. The measurement is performed in lepton+mi>jets> final states using a new kinematic fitting algorithm for events with four or more jets and a new partial reconstruction algorithm for events with only three jets. Corrected for detector acceptance and resolution effects, the asymmetry is evaluated to be mi>AFB>=(10.6±3.0)%. Results are consistent with the standard model predictions which range from 5.0% to 8.8%. We also present the dependence of the asymmetry on the invariant mass of the top quark–antiquark system and the difference in rapidities of the top quark and antiquark.

  8. The expression of miR-125b regulates angiogenesis during the recovery of heat-denatured HUVECs.

    Science.gov (United States)

    Zhou, Situo; Zhang, Pihong; Liang, Pengfei; Huang, Xiaoyuan

    2015-06-01

    In previous studies we found that miR-125b was down-regulated in denatured dermis of deep partial thickness burn patients. Moreover, miR-125b inhibited tumor-angiogenesis associated with the decrease of ERBB2 and VEGF expression in ovarian cancer cells and breast cancer cells, etc. In this study, we investigated the expression patterns and roles of miR-125b during the recovery of denatured dermis and heat-denatured human umbilical vein endothelial cells (HUVECs). Deep partial thickness burns in Sprague-Dawley rats and the heat-denatured cells (52°C, 35 s) were used for analysis. Western blot analysis and real-time PCR were applied to evaluate the expression of miR-125b and ERBB2 and VEGF. The ability of angiogenesis in heat-denatured HUVECs was analyzed by scratch wound healing and tube formation assay after pri-miR-125b or anti-miR-125b transfection. miR-125b expression was time-dependent during the recovery of heat-denatured dermis and HUVECs. Moreover, miR-125b regulated ERBB2 mRNA and Protein Expression and regulated angiogenesis association with regulating the expression of VEGF in heat-denatured HUVECs. Taken together our results show that the expression of miR-125b is time-dependent and miR-125b plays a regulatory role of angiogenesis during wound healing after burns. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  9. Circulating miR-126 and miR-499 reflect progression of cardiovascular disease; correlations with uric acid and ejection fraction

    Directory of Open Access Journals (Sweden)

    Masoud Khanaghaei

    2016-04-01

    Full Text Available BackgroundThe aim of this study was to assess plasma levels of endothelium- and heart-associated microRNAs (miRNAs miR-126 and miR-499, respectively, using quantitative reverse transcriptase polymerase chain reaction.MethodsA two-step analysis was conducted on 75 patients undergoing off-pomp coronary artery bypass graft (CABG surgery. Five biomarkers of inflammation and cardiac injury were assessed in addition to the above-mentioned miRNAs.ResultsPlasma concentrations of miRNAs were found to be significantly correlated with plasma levels of cardiac troponin I (cTnI (miR-499, r 0.49, p~0.002; miR-126, r = 0.30, p~0.001, indicating cardiac damage. Data analysis revealed that miR-499 had higher sensitivity and specificity for cardiac injury than miR-126, which reflects more endothelial activation. Interestingly, a strong correlation was observed between both miRNAs and uric acid (UA levels with ventricular contractility measured as ejection fraction (EF (miR-499/EF%, r = 0.58, p~0.004; UA/EF%, r = -0.6, p~0.006; UA/miR-499, r = -0.34; UA/miR-126, r = 0.5, p~0.01.ConclusionsIn patients undergoing CABG, circulating miR-126/499 is associated with presentation of traditional risk factors and reflects post-operative response to injury. Plasma pool of miRNAs likely reflects extracellular miRNAs which are proportional to intracellular miRNA levels. Therefore, circulating levels of these miRNAs have prognostic implications in detection of higher risk of future cardiovascular events.

  10. Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications—A Twin Study

    Directory of Open Access Journals (Sweden)

    Jette Bork-Jensen

    2014-07-01

    Full Text Available Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT and development of type 2 diabetes (T2D. The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans.

  11. Reclaiming Sámi languages

    DEFF Research Database (Denmark)

    Rasmussen, Torkel; Nolan, John Shaun

    2011-01-01

    , this paper investigates what subsequently happens at the grassroots or micro level. This investigation shows that despite more positive policies, there is a strong sentiment of defeatism with regard to Sámi. Sámi speakers face problems because of the lack of implementation of nationally decided laws...... and for the sake of cultural maintenance, but also for instrumental reasons, i.e. to give their children better opportunities in the labor market where knowledge of Sámi is necessary....

  12. Repertoire of bovine miRNA and miRNA-like small regulatory RNAs expressed upon viral infection.

    Directory of Open Access Journals (Sweden)

    Evgeny A Glazov

    Full Text Available MicroRNA (miRNA and other types of small regulatory RNAs play a crucial role in the regulation of gene expression in eukaryotes. Several distinct classes of small regulatory RNAs have been discovered in recent years. To extend the repertoire of small RNAs characterized in mammals and to examine relationship between host miRNA expression and viral infection we used Illumina's ultrahigh throughput sequencing approach. We sequenced three small RNA libraries prepared from cell line derived from the adult bovine kidney under normal conditions and upon infection of the cell line with Bovine herpesvirus 1. We used a bioinformatics approach to distinguish authentic mature miRNA sequences from other classes of small RNAs and short RNA fragments represented in the sequencing data. Using this approach we detected 219 out of 356 known bovine miRNAs and 115 respective miRNA* sequences. In addition we identified five new bovine orthologs of known mammalian miRNAs and discovered 268 new cow miRNAs many of which are not identifiable in other mammalian genomes and thus might be specific to the ruminant lineage. In addition we found seven new bovine mirtron candidates. We also discovered 10 small nucleolar RNA (snoRNA loci that give rise to small RNA with possible miRNA-like function. Results presented in this study extend our knowledge of the biology and evolution of small regulatory RNAs in mammals and illuminate mechanisms of small RNA biogenesis and function. New miRNA sequences and the original sequencing data have been submitted to miRNA repository (miRBase and NCBI GEO archive respectively. We envisage that these resources will facilitate functional annotation of the bovine genome and promote further functional and comparative genomics studies of small regulatory RNA in mammals.

  13. miRNA Signatures of Insulin Resistance in Obesity.

    Science.gov (United States)

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  14. Generation of miRNA sponge constructs

    NARCIS (Netherlands)

    Kluiver, Joost; Slezak-Prochazka, Izabella; Smigielska-Czepiel, Katarzyna; Halsema, Nancy; Kroesen, Bart-Jan; van den Berg, Anke

    2012-01-01

    MicroRNA (miRNA) sponges are RNA molecules with repeated miRNA antisense sequences that can sequester miRNAs from their endogenous targets and thus serve as a decoy. Stably expressed miRNA sponges are especially valuable for long-term loss-of-function studies and can be used in vitro and in vivo. We

  15. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity.

    Science.gov (United States)

    Wyman, Stacia K; Knouf, Emily C; Parkin, Rachael K; Fritz, Brian R; Lin, Daniel W; Dennis, Lucas M; Krouse, Michael A; Webster, Philippa J; Tewari, Muneesh

    2011-09-01

    Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called "isomiRs" adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including MTPAP, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymes-MTPAP, ZCCHC6, and TUT1-have not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next-generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo.

  16. Affirmative Action: Reservation Seats untuk Perempuan di Parlemen India

    Directory of Open Access Journals (Sweden)

    Evi Yunita Kurniaty

    2015-12-01

    Full Text Available The study aims to help us understand and analyze women's efforts in the policy-making process to increase their political participation in the constitutional and electoral processes. We can also see the extent to which the values rooted in the patriarchal culture in a society and what can be done and reduce them. Affirmative action is carried out in India by applying the system of reservation seats for women in the Indian Parliament. This is done in India is proven to increase the number of women in the Indian Parliament. By the way there are quotas for women as a strategy for accessing the political arena has growing support among MPs. In this study, Indonesia could get a reservation seats of learning about the system is done. To increase the representation in the "area" is very difficult to be touched by a quota system which is run now, it can be done with reservation seats quota to ensure women's representation in parliament.

  17. miRvestigator: web application to identify miRNAs responsible for co-regulated gene expression patterns discovered through transcriptome profiling.

    Science.gov (United States)

    Plaisier, Christopher L; Bare, J Christopher; Baliga, Nitin S

    2011-07-01

    Transcriptome profiling studies have produced staggering numbers of gene co-expression signatures for a variety of biological systems. A significant fraction of these signatures will be partially or fully explained by miRNA-mediated targeted transcript degradation. miRvestigator takes as input lists of co-expressed genes from Caenorhabditis elegans, Drosophila melanogaster, G. gallus, Homo sapiens, Mus musculus or Rattus norvegicus and identifies the specific miRNAs that are likely to bind to 3' un-translated region (UTR) sequences to mediate the observed co-regulation. The novelty of our approach is the miRvestigator hidden Markov model (HMM) algorithm which systematically computes a similarity P-value for each unique miRNA seed sequence from the miRNA database miRBase to an overrepresented sequence motif identified within the 3'-UTR of the query genes. We have made this miRNA discovery tool accessible to the community by integrating our HMM algorithm with a proven algorithm for de novo discovery of miRNA seed sequences and wrapping these algorithms into a user-friendly interface. Additionally, the miRvestigator web server also produces a list of putative miRNA binding sites within 3'-UTRs of the query transcripts to facilitate the design of validation experiments. The miRvestigator is freely available at http://mirvestigator.systemsbiology.net.

  18. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Qiuhong Ji

    Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

  19. -5p and -3p strands of miR-145 and miR-140 during mesenchymal stem cell chondrogenic differentiation.

    Science.gov (United States)

    Kenyon, Jonathan D; Sergeeva, Olga; Somoza, Rodrigo A; Li, Ming; Caplan, Arnold I; Khalil, Ahmad M; Lee, Zhenghong

    2018-04-20

    The chondrogenic differentiation of mesenchymal stem cells (MSCs) is mediated by transcription factors and small non-coding RNAs such as micro-RNAs (miRNAs). Each miRNA is initially transcribed as a long transcript, which matures to produce -5p and -3p strands. It is widely believed that the mature and functional miRNA from any given pre-miRNA, usually the -5p strand, is functional, while the opposing -3p strand is degraded. However, recent cartilage literature started to show functional -3p stands for a few miRNAs. This study aimed at examining both -5p and -3p strands of two key miRNAs miR-140 and miR-145 that are known to be involved in the chondrogenic differentiation of MSCs. The level (copy number) of both -5p and -3p strands of miR-145 and miR-140 along the timeline of MSC chondrogenic differentiation was determined by PCR. The gene expression profiles of several genes related to MSC chondrogenesis were compared with these miRNA profiles along the same timeline. While miR-145-3p is declining in step with miR-145-5p in pellet cultures during the process, the -3p strand is only 1% - 2% of the total miR-145 products. In contrast, the mature -3p and -5p products of miR-140 are found to increase with near equal molar expression throughout chondrogenic differentiation. Numerous genes are expressed by cartilage progenitor cells during development. One such target gene, Sox9 is a regulatory target of the dominant miR-145-5p, consistent with the data. Further experimental validations are warranted to confirm that ACAN, FOXO1 and RUNX3 as direct targets of miR-145-5p in the context of MSC chondrogenesis. Similarly, TRSP1 and ACAN are worth further validation as direct targets of miR-145-3p. For miR-140, SOX4 shall be further validated as a direct target of miR-140-5p while KLF4, PTHLH, and WNT5A can be validated as direct targets of miR-140-3p.

  20. Characterization of the Merkel Cell Carcinoma miRNome

    Directory of Open Access Journals (Sweden)

    Matthew S. Ning

    2014-01-01

    Full Text Available MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs, next-generation sequencing (NGS of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.

  1. miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages.

    Science.gov (United States)

    Liu, Yanhua; Wang, Ruo; Jiang, Jing; Yang, Bingfen; Cao, Zhihong; Cheng, Xiaoxing

    2015-10-01

    Tuberculosis (TB) is a serious infectious disease that most commonly affects the lungs. Macrophages are among the first line defenders against establishment of Mycobacterium tuberculosis infection in the lungs. In this study, we found that activation and cytokine production in monocyte-derived macrophages (MDM) from patients with active TB was impaired. miR-223 expression was significantly elevated in monocytes and MDM from patients with TB compared with healthy controls. To determine the functional role of miR-223 in macrophages, stable miR-223-expressing and miR-223 antisense-expressing U937 cells were established. Compared with empty vector controls, expression of IL-1β, IL-6, TNF-α and IL-12p40 genes was significantly higher in miR-223 antisense-expressing U937 cells, but lower in miR-223-expressing U937 cells. miR-223 can negatively regulate activation of NF-κB by inhibition of p65 phosphorylation and nuclear translocation. It is concluded that miR-223 can regulate macrophage function by inhibition of cytokine production and NF-κB activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24.

    Science.gov (United States)

    Velleman, S G; Harding, R L

    2017-06-01

    Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth. © 2016 Poultry Science Association Inc.

  3. An Indian tribal view of the back end of the nuclear fuel cycle: historical and cultural lessons

    International Nuclear Information System (INIS)

    Tano, M.L.; Powankee, D.; Lester, A.D.

    1995-01-01

    The Nez Perce Tribe, the Confederated Tribes of the Umatilla Indian Reservation and the Yakama Indian Nation have entered into cooperative agreements with the US Department of Energy to oversee the cleanup of the Hanford Reservation. The Mescalero Apache Tribe and the Meadow Lake Tribal Council have come under severe criticism from some ''ideological pure'' Indians and non-Indians for aiding and abetting the violation of Mother Earth by permitting the land to be contaminated by radioactive wastes. This paper suggests that this view of the Indian relationship to nature and the environment is too narrow and describes aspects of Indian religion that support tribal involvement in radioactive waste management. (O.M.)

  4. Analysis of oil-bearing Cretaceous sandstone hydrocarbon reservoirs, exclusive of the Dakota Sandstone, on the Jicarilla Apache Indian Reservation, New Mexico; TOPICAL

    International Nuclear Information System (INIS)

    Ridgley, Jennie; Wright Dunbar, Robyn

    2000-01-01

    This is the Phase One contract report to the United States Department of Energy, United State Geological Survey and the Jicarilla Apache Indian Tribe on the project entitled''Outcrop Analysis of the Cretaceous Mesaverde Group: Jicarilla Apache Reservation, New Mexico.'' Field work for this project was conducted during July and August 1998, at which time fourteen measured sections were described and correlated on or adjacent to Jicarilla Apache Reservation lands. A fifteen section, described east of the main field area, is included in this report, although its distant location precluded use in the correlation's and cross-sections presented herein. Ground-based photo mosaics were shot for much of the exposed Mesaverde outcrop belt and were used to assist in correlation. Outcrop gamma-ray surveys at six of the fifteen measured sections using a GAD-6 scintillometer was conducted. The raw gamma-ray data are included in this report, however, analysis of those data is part of the ongoing Phase Two of this project

  5. miR-21 Is Linked to Glioma Angiogenesis

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Nielsen, Boye Schnack; Aaberg-Jessen, Charlotte

    2016-01-01

    MicroRNA-21 (miR-21) is the most consistently over-expressed microRNA (miRNA) in malignant gliomas. We have previously reported that miR-21 is upregulated in glioma vessels and subsets of glioma cells. To better understand the role of miR-21 in glioma angiogenesis and to characterize miR-21......-localized with the hypoxia- and angiogenesis-associated markers HIF-1α (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate...... with the six markers. These findings suggest that miR-21 is linked to glioma angiogenesis, that miR-21 is unlikely to regulate PTEN, and that miR-21-positive tumor cells do not possess stem cell characteristics....

  6. Impact of Type 2 Myocardial Infarction (MI) on Hospital-Level MI Outcomes: Implications for Quality and Public Reporting.

    Science.gov (United States)

    Arora, Sameer; Strassle, Paula D; Qamar, Arman; Wheeler, Evan N; Levine, Alexandra L; Misenheimer, Jacob A; Cavender, Matthew A; Stouffer, George A; Kaul, Prashant

    2018-03-26

    The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non-ST-segment-elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital-level NSTEMI metrics and discuss the implications for quality and public reporting. We conducted a single-center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan-Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P <0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P <0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67-7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44-2.73) after discharge. Type 2 MI was also associated with a lower 30-day cardiovascular-related readmission (risk ratio: 0.49; 95% confidence interval, 0.12-2.06). NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Meta-analysis using a novel database, miRStress, reveals miRNAs that are frequently associated with the radiation and hypoxia stress-responses.

    Directory of Open Access Journals (Sweden)

    Laura Ann Jacobs

    Full Text Available Organisms are often exposed to environmental pressures that affect homeostasis, so it is important to understand the biological basis of stress-response. Various biological mechanisms have evolved to help cells cope with potentially cytotoxic changes in their environment. miRNAs are small non-coding RNAs which are able to regulate mRNA stability. It has been suggested that miRNAs may tip the balance between continued cytorepair and induction of apoptosis in response to stress. There is a wealth of data in the literature showing the effect of environmental stress on miRNAs, but it is scattered in a large number of disparate publications. Meta-analyses of this data would produce added insight into the molecular mechanisms of stress-response. To facilitate this we created and manually curated the miRStress database, which describes the changes in miRNA levels following an array of stress types in eukaryotic cells. Here we describe this database and validate the miRStress tool for analysing miRNAs that are regulated by stress. To validate the database we performed a cross-species analysis to identify miRNAs that respond to radiation. The analysis tool confirms miR-21 and miR-34a as frequently deregulated in response to radiation, but also identifies novel candidates as potentially important players in this stress response, including miR-15b, miR-19b, and miR-106a. Similarly, we used the miRStress tool to analyse hypoxia-responsive miRNAs. The most frequently deregulated miRNAs were miR-210 and miR-21, as expected. Several other miRNAs were also found to be associated with hypoxia, including miR-181b, miR-26a/b, miR-106a, miR-213 and miR-192. Therefore the miRStress tool has identified miRNAs with hitherto unknown or under-appreciated roles in the response to specific stress types. The miRStress tool, which can be used to uncover new insight into the biological roles of miRNAs, and also has the potential to unearth potential biomarkers for

  8. Cloning and characterization of pre-miR159a and pre-miR1123 from ...

    African Journals Online (AJOL)

    Although many miRNA genes are conserved across the plant species, the same gene family varies significantly in size and genomic organization in different species. ... Sequence identity matrix suggests 43-82% variation in precursor of Tae AL pre-miR159a (Tae Agra local pre-miR159a) across the species. On the other ...

  9. Functional integration of complex miRNA networks in central and peripheral lesion and axonal regeneration.

    Science.gov (United States)

    Ghibaudi, M; Boido, M; Vercelli, A

    2017-11-01

    New players are emerging in the game of peripheral and central nervous system injury since their physiopathological mechanisms remain partially elusive. These mechanisms are characterized by several molecules whose activation and/or modification following a trauma is often controlled at transcriptional level. In this scenario, microRNAs (miRNAs/miRs) have been identified as main actors in coordinating important molecular pathways in nerve or spinal cord injury (SCI). miRNAs are small non-coding RNAs whose functionality at network level is now emerging as a new level of complexity. Indeed they can act as an organized network to provide a precise control of several biological processes. Here we describe the functional synergy of some miRNAs in case of SCI and peripheral damage. In particular we show how several small RNAs can cooperate in influencing simultaneously the molecular pathways orchestrating axon regeneration, inflammation, apoptosis and remyelination. We report about the networks for which miRNA-target bindings have been experimentally demonstrated or inferred based on target prediction data: in both cases, the connection between one miRNA and its downstream pathway is derived from a validated observation or is predicted from the literature. Hence, we discuss the importance of miRNAs in some pathological processes focusing on their functional structure as participating in a cooperative and/or convergence network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Valsartan ameliorates KIR2.1 in rats with myocardial infarction via the NF-κB-miR-16 pathway.

    Science.gov (United States)

    Li, Xinran; Hu, Hesheng; Wang, Ye; Xue, Mei; Li, Xiaolu; Cheng, Wenjuan; Xuan, Yongli; Yin, Jie; Yang, Na; Yan, Suhua

    2016-09-30

    MicroRNAs have an important role in regulating arrhythmogenesis. MicroRNA-16 (miR-16) is predicted to target KCNJ2. The regulation of miR-16 is primarily due to NF-κB. Whether valsartan could downregulate miR-16 via the inhibition of NF-κB after MI and whether miR-16 targets KCNJ2 remain unclear. MI rats received valsartan or saline for 7days. The protein levels of NF-κB p65, inhibitor κBα (IκBα), and Kir2.1 were detected by Western blot analysis. The mRNA levels of Kir2.1 and miR-16 were examined by quantitative real-time PCR. Whole cell patch-clamp techniques were applied to record IK1. MiR-16 expression was higher in the infarct border, and was accompanied by a depressed IK1/KIR2.1 level. Additionally, miR-16 overexpression suppressed KCNJ2/KIR2.1 expression. In contrast, miR-16 inhibition or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-16 target. In the MI rats, compared to saline treatment, valsartan reduced NF-κB p65 and miR-16 expression and increased IκBα and Kir2.1 expression. In vitro, angiotensin II increased miR-16 expression and valsartan inhibited it. Overexpressing miR-16 in cells treated with valsartan abrogated its beneficial effect on KCNJ2/Kir2.1. NF-κB activation directly upregulates miR-16 expression. miR-16 controls KCNJ2 expression, and valsartan ameliorates Kir2.1 after MI partly depending on the NF-κB-miR-16 pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Threshold-dependent repression of SPL gene expression by miR156/miR157 controls vegetative phase change in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Jia He

    2018-04-01

    Full Text Available Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in leaf morphology that occur during vegetative phase change, we measured their abundance in successive leaves and characterized the phenotype of mutations in different MIR156 and MIR157 genes. miR156/miR157 decline rapidly between leaf 1&2 and leaf 3 and decrease more slowly after this point. The amount of miR156/miR157 in leaves 1&2 greatly exceeds the threshold required to specify their identity. Subsequent leaves have relatively low levels of miR156/miR157 and are sensitive to small changes in their abundance. In these later-formed leaves, the amount of miR156/miR157 is close to the threshold required to specify juvenile vs. adult identity; a relatively small decrease in the abundance of miR156/157 in these leaves produces a disproportionately large increase in SPL proteins and a significant change in leaf morphology. miR157 is more abundant than miR156 but has a smaller effect on shoot morphology and SPL gene expression than miR156. This may be attributable to the inefficiency with which miR157 is loaded onto AGO1, as well as to the presence of an extra nucleotide at the 5' end of miR157 that is mis-paired in the miR157:SPL13 duplex. miR156 represses different targets by different mechanisms: it regulates SPL9 by a combination of transcript cleavage and translational repression and regulates SPL13 primarily by translational repression. Our results offer a molecular explanation for the changes in leaf morphology that occur during shoot development in Arabidopsis and provide new insights into the mechanism by which miR156 and miR157 regulate gene expression.

  12. miR482 and Its Isoforms in Plants

    Directory of Open Access Journals (Sweden)

    Abdil Hakan EREN

    2016-09-01

    Full Text Available In plants, miR482 family members are generally 22-nucleotide long, distinguishing from other microRNA (miRNA families by their extraordinary and diverse sequence structures. Studies showed that miRNA482 is related to NBLRR (Nucleotide binding-site leucine-rich repeat genes conferring resistance to disease in plants. There are different coded NB-LRR genes which are considered as the part immune response assisting the recognition of pathogens in plant genomes. NB-LRR proteins are mostly related to effector – triggering immune system against pathogens. The main immune receptors in plants are PRR (Pattern recoginition receptor and R (Resistance proteins. R proteins code for immune system proteins by NB-LRR activity. miR482, miR1448, slmiR2118 and ath-miR472 are disease resistance related miRNAs. In several studies, miR482 was found to be a homolog of miR1448 and phylogenetic analyses showed that miR1448 is formed by tandem duplication of miR482. While suppression of miR482 results in plant susceptibility to pathogens, miR482 was considered to play role in nodulation and mycorrhizal processes of soya roots. Increasing evidences exhibit that miR482 is critical in disease resistance against pathogen attacks.

  13. MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Cañueto, J; Cardeñoso-Álvarez, E; García-Hernández, J L; Galindo-Villardón, P; Vicente-Galindo, P; Vicente-Villardón, J L; Alonso-López, D; De Las Rivas, J; Valero, J; Moyano-Sanz, E; Fernández-López, E; Mao, J H; Castellanos-Martín, A; Román-Curto, C; Pérez-Losada, J

    2017-07-01

    Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters

  14. Mismo field experiment in the equatorial Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Masumoto, Y.; Kuroda, Y.; Katsumata, M.; Mizuno, K.; Takayabu, Y.N.; Yoshizaki, M.; Shareef, A.; Fujiyoshi, Y.; McPhaden, M.J.; Murty, V.S.N.; Shirooka, R; Yasunaga, K.; Yamada, H.; Sato, N.; Ushiyama, T.; Moteki, Q.; Seiki, A.; Fujita, M.; Ando, K.; Hase, H.; Ueki, I; Horii, T.; Yokoyama, C.; Miyakawa, T.

    MISMO FIELD EXPERIMENT IN THE EQUATORIAL INDIAN OCEAN * b y Ku n i o yo n e y a m a , yu K i o ma s u m o t o , yo s h i f u m i Ku r o d a , ma s a K i Ka t s u m a t a , Ke i s u K e mi z u n o , yu K a r i n. ta K a y a b u , ma s a n o r i... yo s h i z a K i , al i sh a r e e f, ya s u s h i fu j i y o s h i , mi c h a e l j. mcPh a d e n , V. s. n. mu r t y , ry u i c h i sh i r o o K a , Ka z u a K i ya s u n a g a , hi r o y u K i ya m a d a , na o K i sa t o , to m o K i us...

  15. An Indian tribal view of the back end of the nuclear fuel cycle: Historical and cultural lessons

    International Nuclear Information System (INIS)

    Tano, M.L.; Reuben, J.H.; Powaukee, D.; Lester, A.D.

    1996-01-01

    Indian tribes of the western United States, including the Nez Perce Tribe, the Confederated Tribes of the Umatilla Indian Reservation, and the Yakama Indian Nation, have entered into cooperative agreements with the U.S. Department of Energy to oversee the cleanup of the Hanford Reservation, in Washington state. These and other tribes considering involvement in nuclear waste management programs have been subjected to severe criticism from some Indians and non-Indians, accusing them of aiding and abetting the violation of Mother Earth by acquiescing in the contamination of lands by radioactive wastes. We'd like to suggest that this view of the Indian relationship to nature and the environment is too narrow. While the purpose of this article is not to suggest that Indian beliefs support the location of waste management facilities on Indian lands, we will describe aspects of Indian religion and culture that support tribal involvement in radioactive waste management and environmental restoration, and participation in radioactive waste management decision making

  16. miRNAs in Alzheimer Disease - A Therapeutic Perspective.

    Science.gov (United States)

    Gupta, Priya; Bhattacharjee, Surajit; Sharma, Ashish Ranjan; Sharma, Garima; Lee, Sang-Soo; Chakraborty, Chiranjib

    2017-01-01

    Alzheimer's disease is a neurodegenerative disorder which generally affects people who are more than 60 years of age. The disease is clinically characterised by dementia, loss of cognitive functions and massive neurodegeneration. The presence of neurofibrilary tangles and amyloid plaques in the hippocampal region of the brain are the hallmarks of the disease. Current therapeutic approaches for the treatment of Alzheimer's disease are symptomatic and disease modifying, none of which provide any permanent solution or cure for the disease. Dysregulation of miRNAs is one of the major causes of neurodegeneration. In the present review, the roles of different miRNAs such as miR-9, miR-107, miR-29, miR-34, miR-181, miR-106, miR-146a, miR132, miR124a, miR153 has been discussed in detail in the pathogenesis of various neurodegenerative diseases with special focus on AD. The probability of miRNAs as an alternative and more sensitive approach for detection and management of the AD has also been discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. The expression of miR-181a-5p and miR-371b-5p in chondrosarcoma.

    Science.gov (United States)

    Mutlu, S; Mutlu, H; Kirkbes, S; Eroglu, S; Kabukcuoglu, Y S; Kabukcuoglu, F; Duymus, T M; ISık, M; Ulasli, M

    2015-07-01

    Chondrosarcomas are malignant tumors of chondrocytes that affect bones and joints, and it represents the third most common type of primary bone tumors. Chondrosarcoma is difficult to treat because it is relatively resistant to both chemotherapy and radiation. Thus, surgery remains the best available treatment. It is important to find new diagnostic markers and improve treatment options. miRNAs are small non-coding transcripts (19-25 nucleotides) that regulate gene expression via targeting complementary sequences within messenger RNAs (mRNAs). miRNAs have been shown to be involved in regulation of many biochemical pathways. Dysregulated expression of many miRNAs has also been associated with multiple human diseases, such as cancer. 18 surgical chondrosarcoma specimens were obtained from patients. RNA extractions were performed from decalcified paraffin embedded tissues. The aim of this study was to investigate the expression levels of miR-181a and miR-371b in patients with chondrosarcoma by using RT-PCR and to evaluate the relationship between these miRNAs and chondrosarcoma. miR-181a was found to be upregulated in chondrosarcoma specimens whereas no significant alteration was found for miR-371b expression. It has been proposed that miRNA expression studies might be used as diagnostic, prognostic marker in cancer. miRNA expression data produced in our study may contribute future chondrosarcoma diagnosis and therapy.

  18. Implications of American Indian gambling for social work research and practice.

    Science.gov (United States)

    Momper, Sandra L

    2010-04-01

    Since the 1988 passage of the Indian Gaming and Regulatory Act (IGRA), American Indian tribal communities have rapidly opened up casinos. American Indian participation in recreational gambling has increased, resulting in an increase in problem and pathological gambling. However, increased revenues from gaming have significantly benefited tribes. Background information on the Supreme Court case that led to passage of the IGRA and subsequently the opening of casinos on Indian reservations is provided. Data are presented on American Indian gambling studies that explore the impact of gambling on the development of problem or pathological gambling among American Indians. Reports and data are presented on the effects of gambling on the socioeconomic development of tribal communities. The implications of American Indian gaming for social work research and practice are discussed.

  19. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

    Science.gov (United States)

    GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

    2016-01-01

    MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

  20. 75 FR 60810 - Indian Entities Recognized and Eligible To Receive Services From the United States Bureau of...

    Science.gov (United States)

    2010-10-01

    ... Indian Colony of California Buena Vista Rancheria of Me-Wuk Indians of California Burns Paiute Tribe of... Tribe of Idaho La Jolla Band of Luiseno Indians, California (formerly the La Jolla Band of Luiseno Mission Indians of the La Jolla Reservation) La Posta Band of Diegueno Mission Indians of the La Posta...

  1. Methylation of miRNA genes and oncogenesis.

    Science.gov (United States)

    Loginov, V I; Rykov, S V; Fridman, M V; Braga, E A

    2015-02-01

    Interaction between microRNA (miRNA) and messenger RNA of target genes at the posttranscriptional level provides fine-tuned dynamic regulation of cell signaling pathways. Each miRNA can be involved in regulating hundreds of protein-coding genes, and, conversely, a number of different miRNAs usually target a structural gene. Epigenetic gene inactivation associated with methylation of promoter CpG-islands is common to both protein-coding genes and miRNA genes. Here, data on functions of miRNAs in development of tumor-cell phenotype are reviewed. Genomic organization of promoter CpG-islands of the miRNA genes located in inter- and intragenic areas is discussed. The literature and our own results on frequency of CpG-island methylation in miRNA genes from tumors are summarized, and data regarding a link between such modification and changed activity of miRNA genes and, consequently, protein-coding target genes are presented. Moreover, the impact of miRNA gene methylation on key oncogenetic processes as well as affected signaling pathways is discussed.

  2. Exploration of miRNA families for hypotheses generation.

    KAUST Repository

    Kamanu, T.K.

    2013-10-15

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  3. MTUS1 tumor suppressor and its miRNA regulators in fibroadenoma and breast cancer.

    Science.gov (United States)

    Kara, Murat; Kaplan, Mehmet; Bozgeyik, Ibrahim; Ozcan, Onder; Celik, Ozgur Ilhan; Bozgeyik, Esra; Yumrutas, Onder

    2016-08-10

    Breast cancer is major public health problem predominantly effects female population. Current therapeutic approaches to deal with breast cancer are still lack of effectiveness. Thus, identifying/developing novel strategies to fight against breast cancer is very important. The frequent deletions at 8p21.3-22 chromosomal location nearby D8S254 marker enabled the discovery of a novel tumor suppressor gene, MTUS1. Subsequently, MTUS1 was demonstrated to be less expressed in a variety cancer types including breast cancer. Also, it is obvious that gene expression is widely regulated by miRNAs. Here, we aimed to report differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues. Dynamic analysis of MTUS1 expression levels and its miRNAs regulators were attained by Fluidigm 96×96 Dynamic Array Expression chips and reactions were performed in Fluidigm BioMark™ HD System qPCR. Consequently, MTUS1 mRNA levels were significantly diminished in breast cancer tissues and elevated in fibroadenoma tissues. Also, among MTUS1 targeting miRNAs, miR-183-5p was identified to be overexpressed in breast cancer and down-regulated in fibroadenoma tissues. Also, expression levels of MTUS1 and miR-183-5p were well correlated with clinical parameters. In particular, MTUS1 expression was found to be diminished and miR-183-5p expression was elevated with the advancing stage. In conclusion, as a potential therapeutic target, miR-183-5p can be a chief regulator of MTUS1 and MTUS1-miR-183-5p axis may have significant influence in the pathology of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Human disease MiRNA inference by combining target information based on heterogeneous manifolds.

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen

    2018-04-01

    The emergence of network medicine has provided great insight into the identification of disease-related molecules, which could help with the development of personalized medicine. However, the state-of-the-art methods could neither simultaneously consider target information and the known miRNA-disease associations nor effectively explore novel gene-disease associations as a by-product during the process of inferring disease-related miRNAs. Computational methods incorporating multiple sources of information offer more opportunities to infer disease-related molecules, including miRNAs and genes in heterogeneous networks at a system level. In this study, we developed a novel algorithm, named inference of Disease-related MiRNAs based on Heterogeneous Manifold (DMHM), to accurately and efficiently identify miRNA-disease associations by integrating multi-omics data. Graph-based regularization was utilized to obtain a smooth function on the data manifold, which constitutes the main principle of DMHM. The novelty of this framework lies in the relatedness between diseases and miRNAs, which are measured via heterogeneous manifolds on heterogeneous networks integrating target information. To demonstrate the effectiveness of DMHM, we conducted comprehensive experiments based on HMDD datasets and compared DMHM with six state-of-the-art methods. Experimental results indicated that DMHM significantly outperformed the other six methods under fivefold cross validation and de novo prediction tests. Case studies have further confirmed the practical usefulness of DMHM. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Characterization and Functional Analysis of Extracellular Vesicles and Muscle-Abundant miRNAs (miR-1, miR-133a, and miR-206 in C2C12 Myocytes and mdx Mice.

    Directory of Open Access Journals (Sweden)

    Yasunari Matsuzaka

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive neuromuscular disorder. Here, we show that the CD63 antigen, which is located on the surface of extracellular vesicles (EVs, is associated with increased levels of muscle-abundant miRNAs, namely myomiRs miR-1, miR-133a, and miR-206, in the sera of DMD patients and mdx mice. Furthermore, the release of EVs from the murine myoblast C2C12 cell line was found to be modulated by intracellular ceramide levels in a Ca2+-dependent manner. Next, to investigate the effects of EVs on cell survival, C2C12 myoblasts and myotubes were cultured with EVs from the sera of mdx mice or C2C12 cells overexpressing myomiRs in presence of cellular stresses. Both the exposure of C2C12 myoblasts and myotubes to EVs from the serum of mdx mice, and the overexpression of miR-133a in C2C12 cells in presence of cellular stress resulted in a significant decrease in cell death. Finally, to assess whether miRNAs regulate skeletal muscle regeneration in vivo, we intraperitoneally injected GW4869 (an inhibitor of exosome secretion into mdx mice for 5 and 10 days. Levels of miRNAs and creatine kinase in the serum of GW4869-treated mdx mice were significantly downregulated compared with those of controls. The tibialis anterior muscles of the GW4869-treated mdx mice showed a robust decrease in Evans blue dye uptake. Collectively, these results indicate that EVs and myomiRs might protect the skeletal muscle of mdx mice from degeneration.

  6. miR398 and miR395 are involved in response to SO2 stress in Arabidopsis thaliana.

    Science.gov (United States)

    Li, Lihong; Yi, Huilan; Xue, Meizhao; Yi, Min

    2017-11-01

    Sulfur dioxide (SO 2 ) is a common air pollutant that has adverse effects on plants. MicroRNAs (miRNAs) are small noncoding RNA that play critical roles in plant development and stress response. In this study, we found that two miRNAs, miR398 and miR395, were differentially expressed in Arabidopsis shoots under SO 2 stress. The expression of miR398 was down-regulated, and the transcript levels of its target genes, Cu/Zn superoxide dismutases (CSD1 and CSD2), were increased during SO 2 exposure. The activity of superoxide dismutase (SOD), one of the major antioxidant enzymes, was enhanced with the increase in the CSD transcript level, suggesting an important role of miR398 in response to SO 2 -induced oxidative stress. Meanwhile, the expression of miR395 was increased, and the transcript levels of its target genes, ATP sulfurylases (APS3 and APS4) and a low-affinity sulfate transporter (SULTR2;1), were decreased in Arabidopsis shoots, showing that miR395 played important roles in the regulation of sulfate assimilation and translocation during SO 2 exposure. The content of glutathione (GSH), an important sulfur-containing antioxidant, was enhanced with the changes in sulfur metabolism in Arabidopsis shoots under SO 2 stress. These results showed that both miR398 and miR395 were involved in protecting plants from oxidative damage during SO 2 exposure. Many stress-responsive cis-elements were found in the promoter regions of MIR398 and MIR395, suggesting that these miRNAs might respond to various environmental conditions, including SO 2 stress. Overall, our study provides an insight into the regulatory roles of miRNAs in response to SO 2 stress in plants, and highlights the molecular mechanisms of plant adaptation to environmental stress.

  7. Survey of Indian issues in the state of New Mexico relating to uranium mining and milling

    International Nuclear Information System (INIS)

    Vandevender, S.G.; Barsumian, L.; Gurbaxani, S.H.

    1979-11-01

    Estimates of Indian uranium resources range from 11 to 50% of the US total resources. About 17% of New Mexico's reserves are known to be on Indian lands. New Mexico has produced almost half of the nation's uranium supply; over half of the known reserves are located within the state. However, the state has virtually no jurisdiction over development of Indian uranium. As a result, economic and environmental impacts on the state are beyond its control. The lack of state and federal control over these impacts is influencing how the Indians allow development to proceed. The impacts of Indian uranium development also influence state control of non-Indian. To the extent that these controls affect the availability of uranium concentrate, DOE needs to understand the issues involved. This issue paper identifies some of the related problems for both the Indians and the state and explores the reasons behind them

  8. miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity.

    Directory of Open Access Journals (Sweden)

    Judit Remenyi

    Full Text Available miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.

  9. Introduction to Indian Ocean biogeochemical processes and ecological variability: Current understanding and emerging perspectives

    Digital Repository Service at National Institute of Oceanography (India)

    Wiggert, J.D.; Hood, R.R.; Naqvi, S.W.A.; Brink, K.H.; Smith, S.L.

    stream_size 35035 stream_content_type text/plain stream_name Geophys_Monogr_Ser_185_1.pdf.txt stream_source_info Geophys_Monogr_Ser_185_1.pdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 � Indian... inter- pretations of zooplankton observations obtained during the JGOFS cruises of the mid-�990s through the use of a food web synthesis that elucidates how mesozooplankton and mi- crozooplankton contribute to carbon flows within the Ara- bian Sea...

  10. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas; Jensen, Taylor J.; Garbe, James C.; Heimark, Ronald L.; Cress, Anne E.; Dickinson, Sally; Stampfer, Martha R.; Futscher, Bernard W.

    2009-12-23

    BACKGROUND: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. METHODOLOGY/ PRINCIPAL FINDINGS: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2'-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control. CONCLUSIONS/ SIGNIFICANCE: We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation

  11. Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption.

    Science.gov (United States)

    Calo, Nicolas; Ramadori, Pierluigi; Sobolewski, Cyril; Romero, Yannick; Maeder, Christine; Fournier, Margot; Rantakari, Pia; Zhang, Fu-Ping; Poutanen, Matti; Dufour, Jean-François; Humar, Bostjan; Nef, Serge; Foti, Michelangelo

    2016-11-01

    miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in early stages of metabolic liver disorders associated with diet-induced obesity (DIO). Constitutive miR-21/miR-21* knockout (miR21KO) and liver-specific miR-21/miR-21* knockout (LImiR21KO) mice were generated. Mice were then fed with high-fat diet (HFD) and alterations of the lipid and glucose metabolism were investigated. Serum and ex vivo explanted liver tissue were analysed. Under normal breeding conditions and standard diet, miR-21/miR-21* deletion in mice was not associated with any detectable phenotypic alterations. However, when mice were challenged with an obesogenic diet, glucose intolerance, steatosis and adiposity were improved in mice lacking miR-21/miR-21* . Deletion of miR-21/miR-21* specifically in hepatocytes led to similar improvements in mice fed an HFD, indicating a crucial role for hepatic miR-21/miR-21* in metabolic disorders associated with DIO. Further molecular analyses demonstrated that miR-21/miR-21* deletion in hepatocytes increases insulin sensitivity and modulates the expression of multiple key metabolic transcription factors involved in fatty acid uptake, de novo lipogenesis, gluconeogenesis and glucose output. Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21 * as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Yukari Takahashi

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.

  13. Evaluation of the miRNA-146a and miRNA-155 Expression Levels in Patients with Oral Lichen Planus.

    Science.gov (United States)

    Ahmadi-Motamayel, Fatemeh; Bayat, Zeynab; Hajilooi, Mehrdad; Shahryar-Hesami, Soroosh; Mahdavinezhad, Ali; Samie, Lida; Solgi, Ghasem

    2017-12-01

    Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2-ΔΔct method. The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than those of healthy controls. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.

  14. Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients.

    Science.gov (United States)

    Roth, Patrick; Keller, Andreas; Hoheisel, Jörg D; Codo, Paula; Bauer, Andrea S; Backes, Christina; Leidinger, Petra; Meese, Eckart; Thiel, Eckhard; Korfel, Agnieszka; Weller, Michael

    2015-02-01

    Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

    Science.gov (United States)

    Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

    2017-07-15

    Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. miRNA array analysis determines miR-205 is overexpressed in head and neck squamous cell carcinoma and enhances cellular proliferation

    Directory of Open Access Journals (Sweden)

    Howard JD

    2013-08-01

    Full Text Available MicroRNAs (miRNAs play a critical role in cell cycle and pro-survival signal regulation. Consequently, their deregulation can enhance tumorigenesis and cancer progression. In the current investigation, we determined whether cancer- or human papillomavirus (HPV-specific miRNA deregulation could further elucidate signal transduction events unique to head and neck squamous cell carcinoma (HNSCC. Twenty-nine newly diagnosed HNSCC tumors (HPV-positive: 14, HPV-negative: 15 and four normal mucosa samples were analyzed for global miRNA expression. Differential miRNA expression analysis concluded HNSCC is characterized by a general upregulation of miRNAs compared to normal mucosa. Additionally, miR-449a and miR-129-3p were statistically significant miRNAs differentially expressed between HPV-positive and HPV-negative HNSCC. The upregulation of miR-449a was also validated within an independent dataset obtained from TCGA containing 279 HNSCCs and 39 normal adjacent mucosa samples. To gain a better understanding of miRNA-mediated cell cycle deregulation in HNSCC, we functionally evaluated miR-205, a transcript upregulated in our cancer-specific analysis and a putative regulator of E2F1. Modulation of miR-205 with a miRNA mimic and inhibitor revealed miR-205 is capable of regulating E2F1 expression in HNSCC and overexpression of this transcript enhances proliferation. This study demonstrates miRNA expression is highly deregulated in HNSCC and functional evaluations of these miRNAs may reveal novel HPV context dependent mechanisms in this disease.

  17. Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2017-01-01

    Full Text Available Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499 were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR. The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression.

  18. Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response.

    Science.gov (United States)

    Fiori, Laura M; Lopez, Juan Pablo; Richard-Devantoy, Stéphane; Berlim, Marcelo; Chachamovich, Eduardo; Jollant, Fabrice; Foster, Jane; Rotzinger, Susan; Kennedy, Sidney H; Turecki, Gustavo

    2017-08-01

    Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response. We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed. In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment. Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

    Science.gov (United States)

    Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

    2016-09-07

    Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. miR-486-3p, miR-139-5p, and miR-21 as Biomarkers for the Detection of Oral Tongue Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zujian Chen

    2017-01-01

    Full Text Available Oral tongue squamous cell carcinoma (TSCC is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA biomarkers for the detection of TSCC. TaqMan array-based microRNA profiling analysis was performed on 10 archived TSCC samples and their matching normal tissues. A panel of 12 differentially expressed microRNAs was identified. Eight of these differentially expressed microRNAs were validated in an independent sample set. A random forest (RF classification model was built with miR-486-3p, miR-139-5p, and miR-21, and it was able to detect TSCC with a sensitivity of 100% and a specificity of 86.7% (overall error rate = 6.7%. As such, this study demonstrated the utility of the archived clinical specimens for microRNA biomarker discovery. The feasibility of using microRNA biomarkers (miR-486-3p, miR-139-5p, and miR-21 for the detection of TSCC was confirmed.

  1. microRNA analysis of Taenia crassiceps cysticerci under praziquantel treatment and genome-wide identification of Taenia solium miRNAs.

    Science.gov (United States)

    Pérez, Matías Gastón; Macchiaroli, Natalia; Lichtenstein, Gabriel; Conti, Gabriela; Asurmendi, Sebastián; Milone, Diego Humberto; Stegmayer, Georgina; Kamenetzky, Laura; Cucher, Marcela; Rosenzvit, Mara Cecilia

    2017-09-01

    MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as important regulators of gene expression and perform critical functions in development and disease. In spite of the increased interest in miRNAs from helminth parasites, no information is available on miRNAs from Taenia solium, the causative agent of cysticercosis, a neglected disease affecting millions of people worldwide. Here we performed a comprehensive analysis of miRNAs from Taenia crassiceps, a laboratory model for T. solium studies, and identified miRNAs in the T. solium genome. Moreover, we analysed the effect of praziquantel, one of the two main drugs used for cysticercosis treatment, on the miRNA expression profile of T. crassiceps cysticerci. Using small RNA-seq and two independent algorithms for miRNA prediction, as well as northern blot validation, we found transcriptional evidence of 39 miRNA loci in T. crassiceps. Since miRNAs were mapped to the T. solium genome, these miRNAs are considered common to both parasites. The miRNA expression profile of T. crassiceps was biased to the same set of highly expressed miRNAs reported in other cestodes. We found a significant altered expression of miR-7b under praziquantel treatment. In addition, we searched for miRNAs predicted to target genes related to drug response. We performed a detailed target prediction for miR-7b and found genes related to drug action. We report an initial approach to study the effect of sub-lethal drug treatment on miRNA expression in a cestode parasite, which provides a platform for further studies of miRNA involvement in drug effects. The results of our work could be applied to drug development and provide basic knowledge of cysticercosis and other neglected helminth infections. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  2. Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy.

    Science.gov (United States)

    Zanotti, Simona; Gibertini, Sara; Curcio, Maurizio; Savadori, Paolo; Pasanisi, Barbara; Morandi, Lucia; Cornelio, Ferdinando; Mantegazza, Renato; Mora, Marina

    2015-07-01

    Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition. Copyright © 2015. Published by Elsevier B.V.

  3. Circulating exosomal miR-27a and miR-130a act as novel diagnostic and prognostic biomarkers of colorectal cancer.

    Science.gov (United States)

    Wang, Shukui; Liu, Xiangxiang; Pan, Bei; Sun, Li; Chen, Xiaoxiang; Zeng, Kaixuan; Hu, Xiuxiu; Xu, Tao; Xu, Mu

    2018-05-08

    Colorectal cancer (CRC) is one of the most common cancers worldwide usually with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific circulating exosomal miRNAs could act as biomarkers for early diagnosis of CRC. A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using quantitative reverse-transcriptase PCR (qRT-PCR) and Receiver operating characteristic (ROC) curve analysis in subsequent training phase, validation phase and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan-Meier method. The expression of exosomal miR-27a and miR-130a in plasma significantly increased in CRC. The area under ROC curves (AUCs) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for CRC (AUCs = 0.846, 0.898 and 0.801 for the training, validation, and external validation phases, respectively). CRC patients with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis. We identified a circulating exosomal miRNAs panel for the detection of CRC. The exosomal miR-27a and miR-130a panel in plasma may act as a non-invasive biomarker for early detection and predicting prognosis of CRC. Copyright ©2018, American Association for Cancer Research.

  4. miR-10 in development and cancer

    DEFF Research Database (Denmark)

    Lund, Anders Henrik

    2010-01-01

    The microRNA (miRNA) miR-10 family has attracted attention because of its conservation and the position of the miR-10 genes within the Hox clusters of developmental regulators. In several species, miR-10 is coexpressed with a set of Hox genes and has been found to regulate the translation of Hox ...... function to the miRNA repertoire.Cell Death and Differentiation advance online publication, 22 May 2009; doi:10.1038/cdd.2009.58....

  5. Bone-related Circulating MicroRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their Association to Bone Microstructure and Histomorphometry.

    Science.gov (United States)

    Feichtinger, Xaver; Muschitz, Christian; Heimel, Patrick; Baierl, Andreas; Fahrleitner-Pammer, Astrid; Redl, Heinz; Resch, Heinrich; Geiger, Elisabeth; Skalicky, Susanna; Dormann, Rainer; Plachel, Fabian; Pietschmann, Peter; Grillari, Johannes; Hackl, Matthias; Kocijan, Roland

    2018-03-20

    The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 μm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.

  6. MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis.

    Science.gov (United States)

    Xu, Longjiang; Leng, Hong; Shi, Xin; Ji, Jiang; Fu, Jinxiang; Leng, Hong

    2017-06-01

    MicroRNAs (miRNAs) have been demonstrated to contribute to malignant progression in psoriasis development. The purposes of the study was to evaluated the effects of miRNA-155 on cell proliferation, migration and apoptosis in psoriasis development via PTEN singaling pathway and identify its direct target protein. Quantitative real-time RT-PCR (qRT-PCR) was performed to examine the level of miR-155 in psoriasis cells, miR-155 was downregulated in a psoriasis cell line Hacat by transfected with small interfering RNA (siRNA), respectively. Cell survival was detected by the MTT assay and colony formation assay. Cell migration and invasion were measured via wound-healing assayand transwell assay. In addition, cell cycle and apoptosis about psoriasis cells was measured by flow cytometry. In this study, qRT-PCR assay showed that the expressions of miR-155 mRNA in psoriasis tissues were significantly higher than that in normal tissues. The assays about cell growth and proliferation showed that miR-155 knockdown led to a significant decrease in cell proliferation which was determined by MTT assay and colony formation assay compared to those of Lv-NC cells. Flow cytometry analysis showed that depletion of miR-155 could cause cell cycle change and the number of apoptotic cells was significantly increased in Lv-miR155 cells compared with control cells. In addition, the expression of several apoptosis-related factors were dramatically changed, such as PTEN, PIP 3 , AKT, p-AKT, Bax and Bcl-2. Our findings indicate that down-regulation of miR-155 significantly inhibits proliferation, migration, invasion and promotes apoptosis through PTEN singaling pathway in psoriasis cells. miR-155 might function as an oncogene miRNA in the progress of psoriasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. The microRNA ame-miR-279a regulates sucrose responsiveness of forager honey bees (Apis mellifera).

    Science.gov (United States)

    Liu, Fang; Shi, Tengfei; Yin, Wei; Su, Xin; Qi, Lei; Huang, Zachary Y; Zhang, Shaowu; Yu, Linsheng

    2017-11-01

    Increasing evidence demonstrates that microRNAs (miRNA) play an important role in the regulation of animal behaviours. Honey bees (Apis mellifera) are eusocial insects, with honey bee workers displaying age-dependent behavioural maturation. Many different miRNAs have been implicated in the change of behaviours in honey bees and ame-miR-279a was previously shown to be more highly expressed in nurse bee heads than in those of foragers. However, it was not clear whether this difference in expression was associated with age or task performance. Here we show that ame-miR-279a shows significantly higher expression in the brains of nurse bees relative to forager bees regardless of their ages, and that ame-miR-279a is primarily localized in the Kenyon cells of the mushroom body in both foragers and nurses. Overexpression of ame-miR-279a attenuates the sucrose responsiveness of foragers, while its absence enhances their sucrose responsiveness. Lastly, we determined that ame-miR-279a directly target the mRNA of Mblk-1. These findings suggest that ame-miR-279a plays important roles in regulating honey bee division of labour. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The Generation of Insulin Producing Cells from Human Mesenchymal Stem Cells by MiR-375 and Anti-MiR-9.

    Science.gov (United States)

    Jafarian, Arefeh; Taghikani, Mohammad; Abroun, Saeid; Allahverdi, Amir; Lamei, Maryam; Lakpour, Niknam; Soleimani, Masoud

    2015-01-01

    MicroRNAs (miRNAs) are a group of endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. A number of studies have led to the notion that some miRNAs have key roles in control of pancreatic islet development and insulin secretion. Based on some studies on miRNAs pattern, the researchers in this paper investigated the pancreatic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) by up-regulation of miR-375 and down-regulation of miR-9 by lentiviruses containing miR-375 and anti-miR-9. After 21 days of induction, islet-like clusters containing insulin producing cells (IPCs) were confirmed by dithizone (DTZ) staining. The IPCs and β cell specific related genes and proteins were detected using qRT-PCR and immunofluorescence on days 7, 14 and 21 of differentiation. Glucose challenge test was performed at different concentrations of glucose so extracellular and intracellular insulin and C-peptide were assayed using ELISA kit. Although derived IPCs by miR-375 alone were capable to express insulin and other endocrine specific transcription factors, the cells lacked the machinery to respond to glucose. It was found that over-expression of miR-375 led to a reduction in levels of Mtpn protein in derived IPCs, while treatment with anti-miR-9 following miR-375 over-expression had synergistic effects on MSCs differentiation and insulin secretion in a glucose-regulated manner. The researchers reported that silencing of miR-9 increased OC-2 protein in IPCs that may contribute to the observed glucose-regulated insulin secretion. Although the roles of miR-375 and miR-9 are well known in pancreatic development and insulin secretion, the use of these miRNAs in transdifferentiation was never demonstrated. These findings highlight miRNAs functions in stem cells differentiation and suggest that they could be used as therapeutic tools for gene-based therapy in diabetes mellitus.

  9. Effects of miRNA-197 overexpression on proliferation, apoptosis and migration in levonorgestrel treated uterine leiomyoma cells.

    Science.gov (United States)

    Wu, Xiaoli; Ling, Jing; Fu, Ziyi; Ji, Chenbo; Wu, Jiangping; Xu, Qing

    2015-04-01

    Uterine leiomyoma is the ahead benign tumor of the female genital tract, which resulted in menstrual abnormalities, recurrent pregnancy loss, and other serious gynecological disorders in women. Recently, as the process of exploring the brief molecular mechanisms of tumorgenesis, microRNAs (miRNAs) have attracted much more attention. In this study, we first confirmed that microRNA-197 (miR-197) was down-regulated significantly in human uterus leiomyoma by quantity real-time polymerase chain reaction, compared to normal uterus myometrium. Then we observed the potential effects of miR-197 overexpression on human uterus leiomyoma cells by cell counting kit 8, wound healing assay, and flow cytometric assessment separately. The data showed that miR-197 could inhibit cell proliferation, induce cell apoptosis, and block cell migration in vitro. Coincidently, levonorgestrel (LNG), a well-known uterus leiomyoma therapy, could induce miR-197 expression in human uterus leiomyoma cells, and over-expression of miR-197 showed a synergy effect on human uterus leiomyoma cell proliferation and apoptosis with LNG. In this study, the data showed that miR-197 could play an anti-oncogenic role in human uterus leiomyoma cells, and cooperate with LNG on the cell proliferation and apoptosis, which suggested that miR-197 might be a potential target and provided database for clinical treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. miR-29b and miR-125a Regulate Podoplanin and Suppress Invasion in Glioblastoma

    Science.gov (United States)

    Cortez, Maria Angelica; Nicoloso, Milena Sabrina; Shimizu, Masayoshi; Rossi, Simona; Gopisetty, Gopal; Molina, Jennifer R.; Carlotti, Carlos; Tirapelli, Daniela; Neder, Luciano; Brassesco, Maria Sol; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga; Georgescu, Maria-Magdalena; Zhang, Wei; Puduvalli, Vinay; Calin, George Adrian

    2017-01-01

    Glioblastoma is the most frequent and malignant brain tumor, characterized by an elevated capacity for cellular proliferation and invasion. Recently, it was demonstrated that podoplanin membrane sialo-glycoprotein encoded by PDPN gene is over-expressed and related to cellular invasion in astrocytic tumors; however the mechanisms of regulation are still unknown. MicroRNAs are noncoding RNAs that regulate gene expression and several biological processes and diseases, including cancer. Nevertheless, their roles in invasion, proliferation, and apoptosis of glioblastoma are not completely understood. In this study, we focused on miR-29b and miR-125a, which were predicted to regulate PDPN, and demonstrated that these microRNAs directly target the 3′ untranslated region of PDPN and inhibit invasion, apoptosis, and proliferation of glioblastomas. Furthermore, we report that miR-29b and miR-125a are downregulated in glioblastomas and also in CD133-positive cells. Taken together, these results suggest that miR-29b and miR-125a represent potential therapeutic targets in glioblastoma. PMID:20665731

  11. Sex selection and health at birth among Indian immigrants.

    Science.gov (United States)

    González, Libertad

    2018-05-01

    I use birth-certificate data for Spain to document extremely son-biased sex ratios at birth among Indian immigrants (122 boys per 100 girls), especially at higher parities. I also show that the children of Indian immigrants display poor health outcomes during infancy. For instance, almost 10% of boys with Indian parents are born prematurely, compared with 6% of boys with native parents. However, there is no evidence of a gender gap in infant health among the children of Indian immigrants. I provide evidence suggesting that the poor outcomes of Indian children at birth may be attributed to the low endowments of Indian mothers, while the absence of a gender gap may be driven by the fact that the parents who would invest less in girls are less likely to carry the pregnancies of girls to term (more likely to practice sex-selective abortion), combined with the lower cost of prenatal investments in Spain (compared with India). Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC).

    Science.gov (United States)

    Song, Mi-Kyung; Ryu, Jae-Chun

    2015-10-01

    To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

    Science.gov (United States)

    ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

    2016-11-15

    The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

  14. Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and Abdominal Aortic Aneurysms

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    Premakumari Venkatesh

    2017-04-01

    Full Text Available Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs and abdominal aortic aneurysms (AAAs compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486-5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm location and common to both thoracic and abdominal pathologies. Thus, changes in miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p impact AAAs. This work validates prior studies on microRNA expression in aneurysmal diseases.

  15. miRTrail - a comprehensive webserver for analyzing gene and miRNA patterns to enhance the understanding of regulatory mechanisms in diseases

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    Laczny Cedric

    2012-02-01

    Full Text Available Abstract Background Expression profiling provides new insights into regulatory and metabolic processes and in particular into pathogenic mechanisms associated with diseases. Besides genes, non-coding transcripts as microRNAs (miRNAs gained increasing relevance in the last decade. To understand the regulatory processes of miRNAs on genes, integrative computer-aided approaches are essential, especially in the light of complex human diseases as cancer. Results Here, we present miRTrail, an integrative tool that allows for performing comprehensive analyses of interactions of genes and miRNAs based on expression profiles. The integrated analysis of mRNA and miRNA data should generate more robust and reliable results on deregulated pathogenic processes and may also offer novel insights into the regulatory interactions between miRNAs and genes. Our web-server excels in carrying out gene sets analysis, analysis of miRNA sets as well as the combination of both in a systems biology approach. To this end, miRTrail integrates information on 20.000 genes, almost 1.000 miRNAs, and roughly 280.000 putative interactions, for Homo sapiens and accordingly for Mus musculus and Danio rerio. The well-established, classical Chi-squared test is one of the central techniques of our tool for the joint consideration of miRNAs and their targets. For interactively visualizing obtained results, it relies on the network analyzers and viewers BiNA or Cytoscape-web, also enabling direct access to relevant literature. We demonstrated the potential of miRTrail by applying our tool to mRNA and miRNA data of malignant melanoma. MiRTrail identified several deregulated miRNAs that target deregulated mRNAs including miRNAs hsa-miR-23b and hsa-miR-223, which target the highest numbers of deregulated mRNAs and regulate the pathway "basal cell carcinoma". In addition, both miRNAs target genes like PTCH1 and RASA1 that are involved in many oncogenic processes. Conclusions The application

  16. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.

    Science.gov (United States)

    Huang, Cheng; Liu, Xue-Jiao; QunZhou; Xie, Juan; Ma, Tao-Tao; Meng, Xiao-Ming; Li, Jun

    2016-03-01

    Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Towards Clinical Applications of Blood-Borne miRNA Signatures: The Influence of the Anticoagulant EDTA on miRNA Abundance.

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    Petra Leidinger

    Full Text Available Circulating microRNAs (miRNAs from blood are increasingly recognized as biomarker candidates for human diseases. Clinical routine settings frequently include blood sampling in tubes with EDTA as anticoagulant without considering the influence of phlebotomy on the overall miRNA expression pattern. We collected blood samples from six healthy individuals each in an EDTA blood collection tube. Subsequently, the blood was transferred into PAXgeneTM tubes at three different time points, i.e. directly (0 min, 10 min, and 2 h after phlebotomy. As control blood was also directly collected in PAXgeneTM blood RNA tubes that contain a reagent to directly lyse blood cells and stabilize their content. For all six blood donors at the four conditions (24 samples we analyzed the abundance of 1,205 miRNAs by human Agilent miRNA V16 microarrays.While we found generally a homogenous pattern of the miRNA abundance in all 24 samples, the duration of the EDTA treatment appears to influence the miRNA abundance of specific miRNAs. The most significant changes are observed after longer EDTA exposition. Overall, the impact of the different blood sample conditions on the miRNA pattern was substantially lower than intra-individual variations. While samples belonging to one of the six individuals mostly cluster together, there was no comparable clustering for any of the four tested blood sampling conditions. The most affected miRNA was miR-769-3p that was not detected in any of the six PAXgene blood samples, but in all EDTA 2h samples. Accordingly, hsa-miR-769-3p was also the only miRNA that showed a significantly different abundance between the 4 blood sample conditions by an ANOVA analysis (Benjamini-Hochberg adjusted p-value of 0.003. Validation by qRT-PCR confirmed this finding.The pattern of blood-borne miRNA abundance is rather homogenous between the four tested blood sample conditions of six blood donors. There was a clustering between the miRNA profiles that belong

  18. Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Paola Ulivi

    2018-01-01

    Full Text Available Targeting angiogenesis in the treatment of colorectal cancer (CRC is a common strategy, for which potential predictive biomarkers have been studied. miRNAs are small non-coding RNAs involved in several processes including the angiogenic pathway. They are very stable in biological fluids, which turns them into potential circulating biomarkers. In this study, we considered a case series of patients with metastatic (m CRC treated with a bevacizumab (B-based treatment, enrolled in the prospective multicentric Italian Trial in Advanced Colorectal Cancer (ITACa. We then analyzed a panel of circulating miRNAs in relation to the patient outcome. In multivariate analysis, circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p resulted in being significantly associated with progression-free survival (PFS (p = 0.027, p = 0.034 and p = 0.039, respectively and overall survival (OS (p = 0.044, p = 0.024 and p = 0.032, respectively. We also observed that an increase in hsa-miR-155-5p at the first clinical evaluation was significantly associated with shorter PFS (HR 3.03 (95% CI 1.06–9.09, p = 0.040 and OS (HR 3.45 (95% CI 1.18–10.00, p = 0.024, with PFS and OS of 9.5 (95% CI 6.8–18.7 and 15.9 (95% CI 8.4–not reached, respectively, in patients with an increase ≥30% of hsa-miR-155-5p and 22.3 (95% CI 10.2–25.5 and 42.9 (24.8–not reached months, respectively, in patients without such increase. In conclusion, our results highlight the potential usefulness of circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p in predicting the outcome of patients with mCRC treated with B. In addition, the variation of circulating hsa-miR-155-5p could also be indicative of the patient survival.

  19. Curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

    Science.gov (United States)

    Liu, Jianbo; Li, Min; Wang, Yuewei; Luo, Jianchao

    2017-08-01

    Curcumin has been reported as a radiosensitizer in prostate cancer. But the underlying mechanism is not well understood. In this study, we firstly assessed how curcumin affects the expression of miR-143/miR-145 cluster. Then, we investigated whether miR-143 is involved in regulation of radiosensitivity and its association with autophagy in prostate cancer cells. Our data showed that PC3, DU145 and LNCaP cells treated with curcumin had significantly restored miR-143 and miR-145 expression. Curcumin showed similar effect as 5-AZA-dC on reducing methylation of CpG dinucleotides in miR-143 promoter. In addition, curcumin treatment reduced the expression of DNMT1 and DNMT3B, which contribute to promoter hypermethylation of the miR-143/miR-145 cluster. Therefore, we infer that curcumin can restore miR-143 and miR-145 expression via hypomethylation. MiR-143 overexpression and curcumin pretreatment enhanced radiation induced cancer cell growth inhibition and apoptosis. MiR-143 and curcumin remarkably reduced radiation-induced autophagy in PC3 and DU145 cells. MiR-143 overexpression alone also reduced the basal level of autophagy in DU145 cells. Mechanistically, miR-143 can suppress autophagy in prostate cancer cells at least via downregulating ATG2B. Based on these findings, we infer that curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

  20. Effects of blue light on flavonoid accumulation linked to the expression of miR393, miR394 and miR395 in longan embryogenic calli.

    Science.gov (United States)

    Li, Hansheng; Lin, Yuling; Chen, Xiaohui; Bai, Yu; Wang, Congqiao; Xu, Xiaoping; Wang, Yun; Lai, Zhongxiong

    2018-01-01

    While flavonoid metabolism's regulation under light conditions by structural genes and transcription factors is understood, the roles of microRNAs (miRNAs) in this pathway have been rarely reported. In this paper, the accurate control of light was firstly enabled through the specially designed plant growth chamber which ensures consistency and accuracy of the cultivation of longan ECs and the repeatability of the experiments. Then, longan ECs were cultured in this chamber for 25 days. The change of growth rate of longan ECs was compared under different light qualities (dark, blue, green, white, green), intensities (16, 32, 64, 128, 256 μmol ·m-2 ·s-1), and durations (8 h, 12 h, 16 h, 20h, 24h). Results indicated that longan ECs had a high growth rate in the condition of blue or green light, at intensity ranged from 16 μmol·m-2·s-1 to 64 μmol·m-2·s-1, and duration from 8 h to 16 h. In addition, the contents of total flavonoids, rutin, and epicatechin were determined. Results indicated that flavonoid contents of longan ECs reached the highest value under blue light, at 32 μmol·m-2·s-1 and 12h/d. Blue light promoted the accumulation of epicatechin, but inhibited the synthesis of rutin. Finally, the expressions of flavonoid pathway genes, miRNAs and target genes were analyzed by qPCR. These results indicated that miR393 and its target gene DlTIR1-3, miR394 and its target gene DlAlMT12, and miR395 and its target gene DlAPS1 had a negative regulating relationship under blue light in longan ECs. Furthermore, miR393, miR394, and miR395 acted on target genes, which negatively regulated flavonoid key genes DlFLS and positively regulated key genes DlCHS, DlCHI, DlF3'H, DlDFR, DlLAR, and finally affected the accumulation of flavonoids. The treatment of longan ECs under the blue light at the intensity of 32 μmol·m-2·s-1 for 12 h/d inhibited the expression of miR393, miR394 and miR395, which promoted the expression of target genes and the accumulation of

  1. Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms.

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    Colleen Marie Bartman

    Full Text Available A wide search for ischemic preconditioning (IPC mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2 to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways. Based on this Per2 dependency, we subsequently found a diurnal expression pattern for miR-21 with higher miR-21 expression levels at Zeitgeber time (ZT 15 compared to ZT3. Gain or loss of function studies for miR-21 using miRNA mimics or miRNA inhibitors and a Seahorse Bioanalyzer uncovered a critical role of miR-21 for cellular glycolysis, glycolytic capacity, and glycolytic reserve. Exposing mice to intense light, a strategy to induce Per2, led to a robust induction of cardiac miR-21 tissue levels and decreased infarct sizes, which was abolished in miR-21-/- mice. Similarly, first translational studies in humans using intense blue light exposure for 5 days in healthy volunteers resulted in increased plasma miR-21 levels which was associated with increased phosphofructokinase activity, the rate-limiting enzyme in glycolysis. Together, we identified miR-21 as cardioprotective downstream target of Per2 and suggest intense light therapy as a potential strategy to enhance miR-21 activity and subsequent carbohydrate metabolism in humans.

  2. Base Composition Characteristics of Mammalian miRNAs

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

  3. 78 FR 26384 - Indian Entities Recognized and Eligible To Receive Services From the United States Bureau of...

    Science.gov (United States)

    2013-05-06

    ... Colony (previously listed as the Bridgeport Paiute Indian Colony of California) Buena Vista Rancheria of...) Kootenai Tribe of Idaho La Jolla Band of Luiseno Indians, California (previously listed as the La Jolla Band of Luiseno Mission Indians of the La Jolla Reservation) La Posta Band of Diegueno Mission Indians...

  4. "We Wanted Those People to See That Indians Aren't Stupid": Identity, Representation, and Resistance in the Cultural Tourism of the Wapato Indian Club

    Science.gov (United States)

    Jacob, Michelle M.

    2012-01-01

    In the 1970s a group of American Indian junior high school students requested that their public school, located on the Yakama Reservation, provide them with opportunities to learn traditional Yakama and powwow-style dancing. They found an advocate in their school counselor, a Yakama woman who helped them form the Wapato Indian Club dance troupe, a…

  5. Making meaning of urban American Indian identity: a multistage integrative process.

    Science.gov (United States)

    Lucero, Nancy M

    2010-10-01

    The cultural identity and tribal connectedness of American Indians are commonly believed to have been negatively affected by the urbanization process in which American Indians have been involved during the past half century. This phenomenological study examined the processes through which cultural identity was formed and maintained by a group of American Indians who had lived since childhood in urban areas, away from their reservations or tribal communities. Seven urban Indian adults, each from a different tribe, shared their experiences related to coming to understand what it means to be American Indian and the development of their American Indian cultural identity. Four themes emerged from participant interviews and were seen to correspond to stages that participants passed through, from their teens through their 30s, that led to understanding and integration of their American Indian identity. Findings point to the importance of considering issues of cultural identity development when providing social work services to urban American Indian young adults.

  6. Conservation and diversification of the miR166 family in soybean and potential roles of newly identified miR166s.

    Science.gov (United States)

    Li, Xuyan; Xie, Xin; Li, Ji; Cui, Yuhai; Hou, Yanming; Zhai, Lulu; Wang, Xiao; Fu, Yanli; Liu, Ranran; Bian, Shaomin

    2017-02-01

    microRNA166 (miR166) is a highly conserved family of miRNAs implicated in a wide range of cellular and physiological processes in plants. miR166 family generally comprises multiple miR166 members in plants, which might exhibit functional redundancy and specificity. The soybean miR166 family consists of 21 members according to the miRBase database. However, the evolutionary conservation and functional diversification of miR166 family members in soybean remain poorly understood. We identified five novel miR166s in soybean by data mining approach, thus enlarging the size of miR166 family from 21 to 26 members. Phylogenetic analyses of the 26 miR166s and their precursors indicated that soybean miR166 family exhibited both evolutionary conservation and diversification, and ten pairs of miR166 precursors with high sequence identity were individually grouped into a discrete clade in the phylogenetic tree. The analysis of genomic organization and evolution of MIR166 gene family revealed that eight segmental duplications and four tandem duplications might occur during evolution of the miR166 family in soybean. The cis-elements in promoters of MIR166 family genes and their putative targets pointed to their possible contributions to the functional conservation and diversification. The targets of soybean miR166s were predicted, and the cleavage of ATHB14-LIKE transcript was experimentally validated by RACE PCR. Further, the expression patterns of the five newly identified MIR166s and 12 target genes were examined during seed development and in response to abiotic stresses, which provided important clues for dissecting their functions and isoform specificity. This study enlarged the size of soybean miR166 family from 21 to 26 members, and the 26 soybean miR166s exhibited evolutionary conservation and diversification. These findings have laid a foundation for elucidating functional conservation and diversification of miR166 family members, especially during seed development or

  7. Phenotypic characterization of miR-92a-/- mice reveals an important function of miR-92a in skeletal development.

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    Daniela Penzkofer

    Full Text Available MicroRNAs (miRNAs, miRs emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a-/- mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a-/- mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a-/- mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.

  8. Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer.

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    Abdel-Rahman N Zekri

    Full Text Available The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs as diagnostic biomarkers in colorectal cancer (CRC and to identify their possibility as candidates for targeted therapy.The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD, 18 with colonic polyps (CP and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016, whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018. On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04.Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223 could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for

  9. Epigenetic architecture and miRNA: reciprocal regulators

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Kjems, Jørgen; Clark, Susan J

    2010-01-01

    Deregulation of epigenetic and microRNA (miRNA) pathways are emerging as key events in carcinogenesis. miRNA genes can be epigenetically regulated and miRNAs can themselves repress key enzymes that drive epigenetic remodeling. Epigenetic and miRNA functions are thus tightly interconnected......RNAs) are considered especially promising in clinical applications, and their biogenesis and function is a subject of active research. In this review, the current status of epigenetic miRNA regulation is summarized and future therapeutic prospects in the field are discussed with a focus on cancer....

  10. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity

    OpenAIRE

    Wyman, Stacia K.; Knouf, Emily C.; Parkin, Rachael K.; Fritz, Brian R.; Lin, Daniel W.; Dennis, Lucas M.; Krouse, Michael A.; Webster, Philippa J.; Tewari, Muneesh

    2011-01-01

    Modification of microRNA sequences by the 3′ addition of nucleotides to generate so-called “isomiRs” adds to the complexity of miRNA function, with recent reports showing that 3′ modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3′ modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications resul...

  11. Adult social roles and alcohol use among American Indians.

    Science.gov (United States)

    Greene, Kaylin M; Eitle, Tamela McNulty; Eitle, David

    2014-09-01

    American Indians are disproportionately burdened by alcohol-related problems. Yet, research exploring predictors of alcohol use among American Indians has been limited by cross-sectional designs and reservation-based samples. Guided by a life course developmental perspective, the current study used a subsample of American Indians (n=927) from the National Longitudinal Study of Adolescent Health (Add Health) to explore alcohol use (current drinking, usual number of drinks, and binge drinking) among this population. We examined whether adult social roles (i.e., cohabitation, marriage, parenthood, college enrollment, and full-time work) were linked to the rise and fall of alcohol use. Multi-level models demonstrated that adult social roles were linked to alcohol use at the within- and between-person levels. Becoming a parent was linked to a lower likelihood of being a current drinker, fewer alcoholic drinks, and less frequent binge drinking. Transitioning to full-time work was associated with a higher likelihood of being a current drinker and more frequent binge drinking. Results point to the importance of exploring within-group trajectories of alcohol use and highlight the protective and risky nature of adult social roles among American Indians. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients

    Directory of Open Access Journals (Sweden)

    Md Sayed Ali Sheikh

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years and 32 unstable CAD (72.03 ± 4.3 years and 20 healthy subjects (71.7 ± 5.2 years, matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.

  13. Mi-spillet

    DEFF Research Database (Denmark)

    Larsen, Lea Lund; Hejlesen, Stine

    2003-01-01

    MI-spillet er et undervisningsspil til folkeskolens mellemtrin og udskolingen. Spillet omformer Howard Gardners teori om de mange intelligenser til et praktisk og håndgribeligt værktøj til brug i folkeskolen. Spillet indeholder et undervisningsmateriale bestående af lærervejledning og kopimappe...... emnebaseret eller tværfagligt arbejde. Alt materialet ligger samlet på en cd-rom, hvorfra materialet printes. Skolen kan derfor ved køb af én cd-rom printe og producere et ubegrænset antal spil. Cd-rommen indeholder: 1. Lærervejledning 2. MI-spillet * Gulvpladerne * Spørgsmål til spillet * Bilag til...

  14. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Natalia Ruiz-Lafuente

    Full Text Available Interleukin 4 (IL-4 induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL cells. MicroRNAs (miRNAs regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC, and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p, miR-500a (3p, miR-502 (3p, and miR-532 (3p and 5p genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

  15. Entropy-based model for miRNA isoform analysis.

    Directory of Open Access Journals (Sweden)

    Shengqin Wang

    Full Text Available MiRNAs have been widely studied due to their important post-transcriptional regulatory roles in gene expression. Many reports have demonstrated the evidence of miRNA isoform products (isomiRs in high-throughput small RNA sequencing data. However, the biological function involved in these molecules is still not well investigated. Here, we developed a Shannon entropy-based model to estimate isomiR expression profiles of high-throughput small RNA sequencing data extracted from miRBase webserver. By using the Kolmogorov-Smirnov statistical test (KS test, we demonstrated that the 5p and 3p miRNAs present more variants than the single arm miRNAs. We also found that the isomiR variant, except the 3' isomiR variant, is strongly correlated with Minimum Free Energy (MFE of pre-miRNA, suggesting the intrinsic feature of pre-miRNA should be one of the important factors for the miRNA regulation. The functional enrichment analysis showed that the miRNAs with high variation, particularly the 5' end variation, are enriched in a set of critical functions, supporting these molecules should not be randomly produced. Our results provide a probabilistic framework for miRNA isoforms analysis, and give functional insights into pre-miRNA processing.

  16. Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls, whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy.

    Science.gov (United States)

    Anastasilakis, Athanasios D; Koulaxis, Dimitrios; Kefala, Nikoleta; Polyzos, Stergios A; Upadhyay, Jagriti; Pagkalidou, Eirini; Economou, Fotios; Anastasilakis, Chrysostomos D; Mantzoros, Christos S

    2017-08-01

    Several myokines are produced by cardiac muscle. We investigated changes in myokine levels at the time of acute myocardial infarction (MI) and following reperfusion in relation to controls. Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable coronary artery disease (CAD) subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and degree of stenosis were recorded. Irisin, follistatin, follistatin-like 3, activin A and B, ALT, AST, CK and CK-MB were measured at baseline and 6 or 24h after the intervention. MI and CAD patients had lower irisin than controls (p<0.001). MI patients had higher follistatin, activin A, CK, CK-MB and AST than CAD patients and controls (all p≤0.001). None of the myokines changed following reperfusion. Circulating irisin was associated with the degree of stenosis in all patients (p=0.05). Irisin was not inferior to CK-MB in predicting MI while folistatin and activin A could discriminate MI from CAD patients with similar to CK-MB accuracy. None of these myokines was altered following PCI in contrast to CK-MB. Irisin levels are lower in MI and CAD implying that their production may depend on myocadial blood supply. Follistatin and activin A are higher in MI than in CAD suggesting increased release due to myocardial necrosis. They can predict MI with accuracy similar to CK-MB and their role in the diagnosis of MI remains to be confirmed by prospective large clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Postpartum Depression Prevention for Reservation-Based American Indians: Results from a Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ginsburg, Golda S.; Barlow, Allison; Goklish, Novalene; Hastings, Ranelda; Baker, Elena Varipatis; Mullany, Britta; Tein, Jenn-Yun; Walkup, John

    2012-01-01

    Background: Postpartum depression is a devastating condition that affects a significant number of women and their offspring. Few preventive interventions have targeted high risk youth, such as American Indians (AIs). Objective: To evaluate the feasibility of a depression prevention program for AI adolescents and young adults. Methods: Expectant AI…

  18. miR-367 regulation of DOC-2/DAB2 interactive protein promotes proliferation, migration and invasion of osteosarcoma cells.

    Science.gov (United States)

    Cai, Wei; Jiang, Haitao; Yu, Yifan; Xu, Yong; Zuo, Wenshan; Wang, Shouguo; Su, Zhen

    2017-11-01

    Recently, miR-367 is reported to exert either oncogenic or tumor suppressive effects in human malignancies. Recent study reports that miR-367 is up-regulated in OS tissues and cell lines, and abrogates adriamycin-induced apoptosis. The clinical significance of miR-367 and its function in OS need further investigation. In our study, miR-367 expression in OS was markedly elevated compared with corresponding non-tumor tissues. High miR-367 expression was associated with malignant clinical features and poor prognosis of OS patients. In accordance, the levels of miR-367 were dramatically up-regulated in OS cells. Loss of miR-367 expression in Saos-2 cells obviously inhibited the proliferation, migration and invasion of cancer cells in vitro. Meanwhile, miR-367 restoration promoted these malignant behaviors of MG-63 cells. Mechanistically, miR-367 negatively regulated DOC-2/DAB2 interactive protein (DAB2IP) abundance in OS cells. Hereby, DAB2IP was recognized as a direct target gene of miR-367 in OS. DAB2IP mRNA level was down-regulated and inversely correlated with miR-367 expression in OS specimens. DAB2IP overexpression prohibited proliferation, migration and invasion in Saos-2 cells, while DAB2IP knockdown showed promoting effects on proliferation, migration and invasion of MG-63 cells. Furthermore, the role of miR-367 might be mediated by DAB2IP-regulated phosphorylation of ERK and AKT in OS cells. To conclude, miR-367 may function as a biomarker for prediction of prognosis and a target for OS therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Treasury Offset Program (TOP) MI

    Data.gov (United States)

    Social Security Administration — The TOP MI helps OPSOS coordinate TOP case processing in the regions. The MI also helped communicate our progress and findings to BFQM and ORDP, as well as the ACOSS.

  20. Athabasca Chipewyan First Nation inquiry : report on WAC Bennett Dam and damage to Indian Reserve no. 201 claim

    International Nuclear Information System (INIS)

    1998-03-01

    Aspects of a claim regarding the WAC Bennett Dam in British Columbia and damage to Indian Reserve 201 are discussed. An inquiry was held to determine whether the Crown owes an outstanding obligation to the Athabasca Chipewyan First Nation regarding damages sustained on their reserve as a result of the construction and operation of the dam. The claim alleges that the drying out of the Peace-Athabasca Delta severely affected the First Nation's treaty rights to hunt, trap and fish for food in the area. It was noted that the dam was constructed in the early 1960s before the establishment of mandatory environmental assessment procedures which are in place today to ensure that projects comply with certain safeguards and minimum standards. In 1971, the Peace-Athabasca Delta Project Group (PADPG) was established to review and to assess the environmental damage caused by the dam. The group was also advised to implement a strategy to mitigate the ongoing environmental deterioration in the Delta. It was concluded that Canada breached its statutory and fiduciary obligations to the Athabasca Chipewyan First nation by failing to take reasonable measures to prevent, to mitigate, or to seek compensation for unjustified infringement on its treaty rights and for environmental damages to IR 201. In this report the Commission recommends that the claim by the Athabasca Chipewyan First Nation be accepted for negotiation under Canada's specific claims policy. figs

  1. Role of miRNA-9 in Brain Development

    Directory of Open Access Journals (Sweden)

    Balachandar Radhakrishnan

    2016-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9 is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon, midbrain, hindbrain, and spinal cord of vertebrate species is highlighted. In the forebrain, miR-9 is necessary for the proper development of dorsoventral telencephalon by targeting marker genes expressed in the telencephalon. It regulates proliferation in telencephalon by regulating Foxg1, Pax6, Gsh2 , and Meis2 genes. The feedback loop regulation between miR-9 and Nr2e1/Tlx helps in neuronal migration and differentiation. Targeting Foxp1 and Foxp2 , and Map1b by miR-9 regulates the radial migration of neurons and axonal development. In the organizers, miR-9 is inversely regulated by hairy1 and Fgf8 to maintain zona limitans interthalamica and midbrain-hindbrain boundary (MHB. It maintains the MHB by inhibiting Fgf signaling genes and is involved in the neurogenesis of the midbrain-hindbrain by regulating Her genes. In the hindbrain, miR-9 modulates progenitor proliferation and differentiation by regulating Her genes and Elav3. In the spinal cord, miR-9 modulates the regulation of Foxp1 and Onecut1 for motor neuron development. In the forebrain, midbrain, and hindbrain, miR-9 is necessary for proper neuronal progenitor maintenance, neurogenesis, and differentiation. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern.

  2. Time-dependent miR-16 serum fluctuations together with reciprocal changes in the expression level of miR-16 in mesocortical circuit contribute to stress resilient phenotype in chronic mild stress - An animal model of depression.

    Science.gov (United States)

    Zurawek, Dariusz; Kusmider, Maciej; Faron-Gorecka, Agata; Gruca, Piotr; Pabian, Paulina; Kolasa, Magdalena; Solich, Joanna; Szafran-Pilch, Kinga; Papp, Mariusz; Dziedzicka-Wasylewska, Marta

    2016-01-01

    MicroRNAs (miRNAs) are involved in stress-related pathologies. However, the molecular mechanisms underlying stress resilience are elusive. Using chronic mild stress (CMS), an animal model of depression, we identified animals exhibiting a resilient phenotype. We investigated serum levels of corticosterone, melatonin and 376 mature miRNAs to find peripheral biomarkers associated with the resilient phenotype. miR-16, selected during screening step, was assayed in different brain regions in order to find potential relationship between brain and peripheral alterations in response to stress. Two CMS experiments that lasted for 2 and 7 consecutive weeks were performed. During both CMS procedures, sucrose consumption levels were significantly decreased in anhedonic-like animals (panimals, whereas the drinking profiles of resilient rats did not change despite the rats being stressed. Serum corticosterone measurements indicated that anhedonic-like animals had blunted hypothalamic-pituitary-adrenal (HPA) axis activity, whereas resilient animals exhibited dynamic responses to stress. miRNA profiling revealed that resilient animals had elevated serum levels of miR-16 after 7 weeks of CMS (adjusted p-valueanimals exhibited reciprocal changes in miR-16 expression level in mesocortical pathway after 2 weeks of CMS (panimals can actively cope with stress on a biochemical level and miR-16 may contribute to a "stress-resistant" behavioral phenotype by pleiotropic modulation of the expression of genes involved in the function of the nervous system. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  3. 25 CFR 213.17 - Government reserves right to purchase minerals produced.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Government reserves right to purchase minerals produced... Leases § 213.17 Government reserves right to purchase minerals produced. In time of war or other public... prevailing market price on the date of sale all or any part of the minerals produced under any lease. Rents...

  4. Circular RNA and miR-7 in Cancer

    DEFF Research Database (Denmark)

    Hansen, Thomas Birkballe; Kjems, Jørgen; Damgaard, Christian Kroun

    2013-01-01

    MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks....... Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance...... the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor....

  5. miRNAs in Normal and Malignant Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Ryutaro Kotaki

    2017-07-01

    Full Text Available Lineage specification is primarily regulated at the transcriptional level and lineage-specific transcription factors determine cell fates. MicroRNAs (miRNAs are 18–24 nucleotide-long non-coding RNAs that post-transcriptionally decrease the translation of target mRNAs and are essential for many cellular functions. miRNAs also regulate lineage specification during hematopoiesis. This review highlights the roles of miRNAs in B-cell development and malignancies, and discusses how miRNA expression profiles correlate with disease prognoses and phenotypes. We also discuss the potential for miRNAs as therapeutic targets and diagnostic tools for B-cell malignancies.

  6. Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling Pathway: A Possible Role in Prevention of Glioma Development.

    Science.gov (United States)

    Rouigari, Maedeh; Dehbashi, Moein; Ghaedi, Kamran; Pourhossein, Meraj

    2018-07-01

    For the first time, we used molecular signaling pathway enrichment analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin pathway. In this prospective study, Validated and predicted targets (targetome) of miR-126 were collected following searching miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases, respectively. Then, approximate expression of miR-126 targeting in Glioma tissue was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In silico molecular pathway enrichment analysis was carried out by DAVID 6.7 database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is related to miR-126 targeting and how miR-126 attributes to glioma development. MiR-126 exerts a variety of functions in cancer pathogenesis via suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and VEGF. Our bioinformatic studies implementing DAVID database, showed the involvement of miR-126 target genes in several signaling pathways including cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function, focal adhesion production, chemokine synthesis and secretion and regulation of the actin cytoskeleton. Taken together, we concluded that miR-126 enhances the formation of glioma cancer stem cell probably via down regulation of IRS-1 in neurotrophin signaling pathway. Copyright© by Royan Institute. All rights reserved.

  7. Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development.

    Science.gov (United States)

    Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Le Luo; Griebel, Philip

    2015-07-01

    Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period. Furthermore, there is limited knowledge regarding the possible role the commensal microbiome may play in regulating mucosal miRNAs expression, although evidence is emerging that a variety of enteric pathogens influence miRNA expression. The current review focuses on recent information that miRNAs play an important role in regulating early development of the bovine mucosal immune system. A possible role for the commensal microbiome in regulating mucosal development by altering miRNA expression is also discussed. Finally, we explore the potential advantages of using the newborn calf as a model to determine how interactions between developmental programming, maternal factors in colostrum, and colonization of the gastrointestinal tract by commensal bacteria may alter mucosal miRNA expression and immune development. Identifying the key factors that regulate mucosal miRNA expression is critical for understanding how the balance between protective immunity and inflammation is maintained to ensure optimal gastrointestinal tract function and health of the whole organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. miReg: a resource for microRNA regulation

    Directory of Open Access Journals (Sweden)

    Barh Debmalya

    2010-03-01

    Full Text Available MicroRNAs (miRNAs/miRs are important cellular components that regulate gene expression at posttranscriptional level. Various upstream components regulate miR expression and any deregulation causes disease conditions. Therefore, understanding of miR regulatory network both at upstream and downstream level is crucial and a resource on this aspect will be helpful. Currently available miR databases are mostly related to downstream targets, sequences, or diseases. But as of now, no database is available that provides a complete picture of miR regulation in a specific condition.

  9. Barriers and facilitators to being physically active on a rural U.S. Northern Plains American Indian reservation.

    Science.gov (United States)

    Jahns, Lisa; McDonald, Leander R; Wadsworth, Ann; Morin, Charles; Liu, Yan

    2014-11-21

    The objective of the present study was to identify barriers to and facilitators of physical activity among American Indian adults living on a rural, U.S. Northern Plains reservation using the nominal group technique (NGT). NGT is a method of data generation and interpretation that combines aspects of qualitative (free generation of responses) and quantitative (systematic ranking of responses) methodologies. Adults participated in one of two NGT sessions asking about either barriers to (n = 6), or facilitators of (n = 5), being physically active. Participants nominated and ranked 21 barriers and 18 facilitators. Barriers indicated lack of knowledge of how to fit physical activity into a daily schedule, work, caring for family members, and prioritizing sedentary pursuits. Other responses included environmental barriers such as lack of access and transportation to a gym, unsafe walking conditions, and inclement weather. Facilitators to following recommendations included knowledge of health benefits of physical activity and the perception of physical activity as enjoyable, including feeling good when working out. Environmental facilitators included being outdoors walking and biking as well as parks and exercise facilities. Responses provided direction for locally designed community-based programs to promote facilitators and decrease barriers to individual's engagement in physical activity.

  10. Identification and expression analysis of miR-144-5p and miR-130b-5p in dairy cattle

    Directory of Open Access Journals (Sweden)

    Z. Li

    2017-07-01

    Full Text Available MicroRNAs (miRNAs can coordinate the main pathways involved in innate and adaptive immune responses by regulating gene expression. To explore the resistance to mastitis in cows, miR-144-5p and miR-130b-5p were identified in bovine mammary gland tissue and 14 potential target genes belonging to the chemokine signaling pathway, the arginine and proline metabolism pathway and the mRNA surveillance pathway were predicted. Subsequently, we estimated the relative expression of miR-144-5p and miR-130b-5p in cow mammary tissues by using stem-loop quantitative real-time polymerase chain reaction. The results showed that the relative expression of miR-144-5p and miR-130b-5p in the mastitis-infected mammary tissues (n = 5 was significantly downregulated 0.14-fold (p < 0. 01 and upregulated 3.34-fold (p < 0. 01, respectively, compared to healthy tissues (n = 5. Our findings reveal that miR-144-5p and miR-130b-5p may have important roles in resistance to mastitis in dairy cattle.

  11. Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

    Science.gov (United States)

    Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

    2016-04-01

    Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Small RNA profiling reveals important roles for miRNAs in Arabidopsis response to Bacillus velezensis FZB42.

    Science.gov (United States)

    Xie, Shanshan; Jiang, Haiyang; Xu, Zhilan; Xu, Qianqian; Cheng, Beijiu

    2017-09-20

    Bacillus velezensis FZB42 (previously classified as Bacillus amyloliquefaciens FZB42) has been confirmed to successfully colonize plant roots and enhance defense response against pathogen infection. This study indicated that FZB42 inoculation enhanced Arabidopsis defense response against Pseudomonas syringae DC3000 through inducing the expression of PR1, PDF1.2 and stomata closure. To further clarify the induced defense response at miRNA level, sRNA libraries from Arabidopsis roots inoculated with FZB42 and control were constructed and sequenced. The reads of 21nt and 24nt in length were the most abundant groups in FZB42-treated library and control library, respectively. 234 known miRNAs and 16 novel miRNAs were identified. Among them, 11 known miRNAs and 4 novel miRNAs were differentially expressed after FZB42 inoculation. Moreover cis-elements (TC-rich repeats, TCA-element and CGTCA-motif) associated with plant defense were also found in the promoters of these miRNAs. Additionally, 141 mRNAs were predicted as potential targets of these differentially expressed miRNAs. GO annotations of the target genes indicated their potential roles in polyamine biosynthetic process and intracellular protein transport biological process, which may contribute to increased defense response. Our findings indicated that Bacillus velezensis FZB42 inoculation altered the expression of Arabidopsis miRNAs and their target genes, which were associated with defense response. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Teen Pregnancy Prevention Program Recommendations from Urban and Reservation Northern Plains American Indian Community Members

    Science.gov (United States)

    McMahon, Tracey R.; Hanson, Jessica D.; Griese, Emily R.; Kenyon, DenYelle Baete

    2015-01-01

    Despite declines over the past few decades, the United States has one of the highest rates of teen pregnancy compared to other industrialized nations. American Indian youth have experienced higher rates of teen pregnancy compared to the overall population for decades. Although it's known that community and cultural adaptation enhance program…

  14. Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

    Science.gov (United States)

    Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

    2018-03-01

    A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. American Indian Women and Cardiovascular Disease

    Science.gov (United States)

    Struthers, Roxanne; Savik, Kay; Hodge, Felicia Schanche

    2011-01-01

    Cardiovascular disease (CVD) is currently the number one killer of American women. Consequently, CVD is a concern for all women, including ethnic women. However, little is known about CVD behaviors and responses to CVD symptomology among minority women, especially American Indian women. Response behaviors to chest pain require important actions. This article examines response behaviors to chest pain in a group of American Indian women participants of the Inter-Tribal Heart Project. In 1992 to 1994, 866 American Indian women, aged 22 years and older, participated in face-to-face interviews to answer survey questions on multiple areas related to cardiovascular disease on 3 rural reservations in Minnesota and Wisconsin. A secondary data analysis was conducted on selected variables including demographic characteristics, healthcare access, rating of health status, personal and family history of cardiovascular disease, and action in response to crushing chest pain that lasted longer than 15 minutes. Research findings report that 68% of women would actively seek healthcare immediately if experiencing crushing chest pain that lasted longer than 15 minutes. However, 264 women (32%) would take a passive action to crushing chest pain, with 23% reporting they would sit down and wait until it passed. Analysis revealed women reporting a passive response were younger in age (under age 45) and had less education (less than a high school education). These findings have implications for nurses and other healthcare providers working in rural, geographically isolated Indian reservations. How to present CVD education in a culturally appropriate manner remains a challenge. PMID:15191257

  16. Marine biosphere reserves - Need of the 21st century

    Digital Repository Service at National Institute of Oceanography (India)

    Dhargalkar, V.K.; Untawale, A.G.

    been declared in India and a few more are under consideration. The present article gives in brief the status of Marine Biosphere Reserves in India and a few other potential areas for the same reason, along the Indian coast. An action plan has been...

  17. Viruses and miRNAs: More Friends than Foes.

    Science.gov (United States)

    Bruscella, Patrice; Bottini, Silvia; Baudesson, Camille; Pawlotsky, Jean-Michel; Feray, Cyrille; Trabucchi, Michele

    2017-01-01

    There is evidence that eukaryotic miRNAs (hereafter called host miRNAs) play a role in the replication and propagation of viruses. Expression or targeting of host miRNAs can be involved in cellular antiviral responses. Most times host miRNAs play a role in viral life-cycles and promote infection through complex regulatory pathways. miRNAs can also be encoded by a viral genome and be expressed in the host cell. Viral miRNAs can share common sequences with host miRNAs or have totally different sequences. They can regulate a variety of biological processes involved in viral infection, including apoptosis, evasion of the immune response, or modulation of viral life-cycle phases. Overall, virus/miRNA pathway interaction is defined by a plethora of complex mechanisms, though not yet fully understood. This article review summarizes recent advances and novel biological concepts related to the understanding of miRNA expression, control and function during viral infections. The article also discusses potential therapeutic applications of this particular host-pathogen interaction.

  18. Leadership Preferences of Indian and Non-Indian Athletes.

    Science.gov (United States)

    Malloy, D. C.; Nilson, R. N.

    1991-01-01

    Among 86 Indian and non-Indian volleyball competitors, non-Indian players indicated significantly greater preferences for leadership that involved democratic behavior, autocratic behavior, or social support. Indians may adapt their behavior by participating in non-Indian games, without changing their traditional value orientations. Contains 22…

  19. miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.

    Science.gov (United States)

    Wu, Qingwei; Zhao, Yingying; Wang, Peihua

    2018-03-01

    This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Cellular microRNA-miR-548g-3p modulates the replication of dengue virus.

    Science.gov (United States)

    Wen, Weitao; He, Zhenjian; Jing, Qinlong; Hu, Yiwen; Lin, Cuiji; Zhou, Rui; Wang, Xiaoqun; Su, Yangfan; Yuan, Jiehao; Chen, Zhenxin; Yuan, Jie; Wu, Jueheng; Li, Jun; Zhu, Xun; Li, Mengfeng

    2015-06-01

    It has been well recognized that microRNA plays a role in the host-pathogen interaction network. The significance of microRNA in the regulation of dengue virus (DENV) replication, however, remains unknown. The objective of our study was to determine the biological function of miR-548g-3p in modulating the replication of dengue virus. Here we report that employment of a microRNA target search algorithm to analyze the 5' untranslated region (5'UTR) consensus sequences of DENV (DENV serotypes 1-4) led to a discovery that miR-548g-3p directly targets the stem loop A promoter element within the 5'UTR, a region essential for DENV replication. Real-time PCR was used to measure the expression levels of miR-548g-3p under DENV infection. We performed overexpression and inhibition assays to test the role of miR-548g-3p on DENV replication. The protein and mRNA levels of interferon were measured by ELISA and real-time PCR respectively. We found that overexpression of miR-548g-3p suppressed multiplication of DENV 1, 2, 3 and 4, and that miR-548g-3p was also found to interfere with DENV translation, thereby suppressing the expression of viral proteins. Our results suggest that miR-548g-3p directly regulates DENV replication and warrant further study to investigate the feasibility of microRNA-based anti-DENV approaches. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  1. [Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients].

    Science.gov (United States)

    Tornero-Esteban, P; Hoyas, J A; Villafuertes, E; Garcia-Bullón, I; Moro, E; Fernández-Gutiérrez, B; Marco, F

    2014-01-01

    MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone. The aim of this study was to determine a possible relationship between the expression of miR-335 and osteoarthritis. MSCs obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically and functionally characterised in a 3-step culture. Expression levels of miR-335 and the mesoderm-specific transcript gene -MEST- that controls its expression were determined by quantitative PCR. Differences in the expression levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and 3.85 [3.20-5.67] were detected between MSCs isolated from patients with osteoarthritis and controls. Although the differences detected did not reach statistical significance (P=.1), a clear trend towards lower expression of miR-335 in osteoarthritis MSCs was observed. Given that miR-335 has the different genes involved in the Wnt signalling pathway as potential targets, the observed trend may help to ascertain, at least partially, some of the alterations which determine the onset or progression of osteoarthritis, and can therefore serve for the design of future therapeutic targets for the treatment of this disease. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  2. Down-regulation of the miR-543 alleviates insulin resistance through targeting the SIRT1.

    Science.gov (United States)

    Hu, Xiaojing; Chi, Liyi; Zhang, Wentao; Bai, Tiao; Zhao, Wei; Feng, Zhanbin; Tian, Hongyan

    2015-12-25

    Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin-resistant HepG2 cells induced by TNF-α. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR-543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3β. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Wind Resource and Feasibility Assessment Report for the Lummi Reservation

    Energy Technology Data Exchange (ETDEWEB)

    DNV Renewables (USA) Inc.; J.C. Brennan & Associates, Inc.; Hamer Environmental L.P.

    2012-08-31

    This report summarizes the wind resource on the Lummi Indian Reservation (Washington State) and presents the methodology, assumptions, and final results of the wind energy development feasibility assessment, which included an assessment of biological impacts and noise impacts.

  4. Political Status of Native Indian Women: Contradictory Implications of Canadian State Policy.

    Science.gov (United States)

    Fiske, Jo-Anne

    1995-01-01

    Explores the ambiguous nature of Canadian Native women's political status in relation to men within the internal political processes of Indian reserve communities. Examines linkages among economic factors, domestic organization, and political process, and the disruption of Indian women's lives by state intervention (particularly federal laws…

  5. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    LENUS (Irish Health Repository)

    Bray, Isabella

    2009-01-01

    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  6. MicroRNA hsa-miR-29b potentiates etoposide toxicity in HeLa cells via down-regulation of Mcl-1.

    Science.gov (United States)

    Kollinerová, S; Dostál, Z; Modrianský, M

    2017-04-01

    Etoposide is commonly used as a monotherapy or in combination with other drugs for cancer treatments. In order to increase the drug efficacy, ceaseless search for novel combinations of drugs and supporting molecules is under way. MiRNAs are natural candidates for facilitating drug effect in various cell types. We used several systems to evaluate the effect of miR-29 family on etoposide toxicity in HeLa cells. We show that miR-29b significantly increases etoposide toxicity in HeLa cells. Because Mcl-1 protein has been recognized as a miR-29 family target, we evaluated downregulation of Mcl-1 protein splicing variant expression induced by miR-29 precursors and confirmed a key role of Mcl-1 protein in enhancing etoposide toxicity. Despite downregulation of Mcl-1 by all three miR-29 family members, only miR-29b significantly enhanced etoposide toxicity. We hypothesized that this difference may be linked to the change in Mcl-1L/Mcl-1S ratio induced by miR-29b. We hypothesized that the change could be due to miR-29b nuclear shuttling. Using specifically modified miR-29b sequences with enhanced cytosolic and nuclear localization we show that there is a difference, albeit statistically non-significant. In conclusion, we show that miR-29b has the synergistic effect with etoposide treatment in the HeLa cells and that this effect is linked to Mcl-1 protein expression and nuclear shuttling of miR-29b. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

    Directory of Open Access Journals (Sweden)

    Qian Cheng

    2017-01-01

    Full Text Available Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs via conveying microRNAs (miRs. miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6 secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line exosomes (OPM2-exo on regulating the proliferation, cancer-associated fibroblast (CAF transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP, α-smooth muscle actin (α-SMA, and stromal-derived factor 1 (SDF-1 expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

  8. New miRNA labeling method for bead-based quantification

    Directory of Open Access Journals (Sweden)

    Lanfranchi Gerolamo

    2010-06-01

    Full Text Available Abstract Background microRNAs (miRNAs are small single-stranded non-coding RNAs that act as crucial regulators of gene expression. Different methods have been developed for miRNA expression profiling in order to better understand gene regulation in normal and pathological conditions. miRNAs expression values obtained from large scale methodologies such as microarrays still need a validation step with alternative technologies. Results Here we have applied with an innovative approach, the Luminex® xMAP™ technology validate expression data of differentially expressed miRNAs obtained from high throughput arrays. We have developed a novel labeling system of small RNA molecules (below 200 nt, optimizing the sensitive cloning method for miRNAs, termed miRNA amplification profiling (mRAP. The Luminex expression patterns of three miRNAs (miR-23a, miR-27a and miR-199a in seven different cell lines have been validated by TaqMan miRNA assay. In all cases, bead-based meas were confirmed by the data obtained by TaqMan and microarray technologies. Conclusions We demonstrate that the measure of individual miRNA by the bead-based method is feasible, high speed, sensitive and low cost. The Luminex® xMAP™ technology also provides flexibility, since the central reaction can be scaled up with additional miRNA capturing beads, allowing validation of many differentially expressed miRNAs obtained from microarrays in a single experiment. We propose this technology as an alternative method to qRT-PCR for validating miRNAs expression data obtained with high-throughput technologies.

  9. MicroRNA-Mediated Rescue of Fear Extinction Memory by miR-144-3p in Extinction-Impaired Mice.

    Science.gov (United States)

    Murphy, Conor P; Li, Xiang; Maurer, Verena; Oberhauser, Michael; Gstir, Ronald; Wearick-Silva, Luis Eduardo; Viola, Thiago Wendt; Schafferer, Simon; Grassi-Oliveira, Rodrigo; Whittle, Nigel; Hüttenhofer, Alexander; Bredy, Timothy W; Singewald, Nicolas

    2017-06-15

    MicroRNA (miRNA)-mediated control of gene expression suggests that miRNAs are interesting targets and/or biomarkers in the treatment of anxiety- and trauma-related disorders, where often memory-associated gene expression is adversely affected. The role of miRNAs in the rescue of impaired fear extinction was assessed using the 129S1/SvlmJ (S1) mouse model of impaired fear extinction. miRNA microarray analysis, reverse transcription polymerase chain reaction, fluorescent in situ hybridization, lentiviral overexpression, and Luciferase reporter assays were used to gain insight into the mechanisms underlying miRNA-mediated normalization of deficient fear extinction. Rescuing impaired fear extinction via dietary zinc restriction was associated with differential expression of miRNAs in the amygdala. One candidate, miR-144-3p, robustly expressed in the basolateral amygdala, showed specific extinction-induced, but not fear-induced, increased expression in both extinction-rescued S1 mice and extinction-intact C57BL/6 (BL6) mice. miR-144-3p upregulation and effects on subsequent behavioral adaption was assessed in S1 and BL6 mice. miR-144-3p overexpression in the basolateral amygdala rescued impaired fear extinction in S1 mice, led to enhanced fear extinction acquisition in BL6 mice, and furthermore protected against fear renewal in BL6 mice. miR-144-3p targets a number of genes implicated in the control of plasticity-associated signaling cascades, including Pten, Spred1, and Notch1. In functional interaction studies, we revealed that the miR-144-3p target, PTEN, colocalized with miR-144-3p in the basolateral amygdala and showed functional downregulation following successful fear extinction in S1 mice. These findings identify a fundamental role of miR-144-3p in the rescue of impaired fear extinction and suggest this miRNA as a viable target in developing novel treatments for posttraumatic stress disorder and related disorders. Copyright © 2017 Society of Biological

  10. Dynamics of miRNA biogenesis and nuclear transport

    Directory of Open Access Journals (Sweden)

    Kotipalli Aneesh

    2016-12-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNA sequences ~22 nucleotides in length that play an important role in gene regulation-transcription and translation. The processing of these miRNAs takes place in both the nucleus and the cytoplasm while the final maturation occurs in the cytoplasm. Some mature miRNAs with nuclear localisation signals (NLS are transported back to the nucleus and some remain in the cytoplasm. The functional roles of these miRNAs are seen in both the nucleus and the cytoplasm. In the nucleus, miRNAs regulate gene expression by binding to the targeted promoter sequences and affect either the transcriptional gene silencing (TGS or transcriptional gene activation (TGA. In the cytoplasm, targeted mRNAs are translationally repressed or cleaved based on the complementarity between the two sequences at the seed region of miRNA and mRNA. The selective transport of mature miRNAs to the nucleus follows the classical nuclear import mechanism. The classical nuclear import mechanism is a highly regulated process, involving exportins and importins. The nuclear pore complex (NPC regulates all these transport events like a gate keeper. The half-life of miRNAs is rather low, so within a short time miRNAs perform their function. Temporal studies of miRNA biogenesis are, therefore, useful. We have carried out simulation studies for important miRNA biogenesis steps and also classical nuclear import mechanism using ordinary differential equation (ODE solver in the Octave software.

  11. Role of Kallistatin Treatment in Aging and Cancer by Modulating miR-34a and miR-21 Expression

    Directory of Open Access Journals (Sweden)

    Julie Chao

    2017-01-01

    Full Text Available Kallistatin is an endogenous protein that regulates differential signaling pathways and a wide spectrum of biological activities via its two structural elements: an active site and a heparin-binding domain. Kallistatin via its heparin-binding site inhibits vascular inflammation and oxidative stress by antagonizing TNF-α-induced NADPH oxidase activity, NF-κB activation, and inflammatory gene expression in endothelial cells. Moreover, kallistatin via its active site inhibits microRNA-34a (miR-34a synthesis and stimulates eNOS and SIRT1 expression in endothelial progenitor cells, whereas its heparin-binding site is crucial for blocking TNF-α-induced miR-21 expression and oxidative stress, thus reducing cellular senescence. By downregulating miR-34a and miR-21 expression, kallistatin treatment attenuates oxidative damage and aortic senescence in streptozotocin-induced diabetic mice and extends Caenorhabditis elegans lifespan under stress conditions. Likewise, kallistatin through the heparin-binding site inhibits TGF-β-induced miR-21 synthesis and oxidative stress in endothelial cells, resulting in inhibition of endothelial-mesenchymal transition, a process contributing to fibrosis and cancer. Furthermore, kallistatin’s active site is essential for stimulating miR-34a and p53 expression and inhibiting the miR-21-Akt-Bcl-2 signaling pathway, thus inducing apoptosis in breast cancer cells. These findings reveal novel mechanisms of kallistatin in protection against senescence, aging, and cancer development by modulating miR-34a and miR-21 levels and inhibiting oxidative stress.

  12. Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A. [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Pustylnyak, Yuliya A. [Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); Pustylnyak, Vladimir O., E-mail: pustylnyak@ngs.ru [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); The Institute International Tomography Center of the Russian Academy of Sciences, Institutskaya str. 3-A, Novosibirsk 630090 (Russian Federation)

    2015-10-01

    MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

  13. Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

    International Nuclear Information System (INIS)

    Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.; Pustylnyak, Yuliya A.; Pustylnyak, Vladimir O.

    2015-01-01

    MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

  14. Association of American Indian cultural identity with physical activity.

    Science.gov (United States)

    Duncan, Glen E; McDougall, Casey L; Dansie, Elizabeth; Garroutte, Eva; Buchwald, Dedra; Henderson, Jeffrey A

    2014-01-01

    Cultural factors are associated with health behaviors among American Indians. Accordingly, the objective of our study was to investigate whether cultural identity, defined as the primary language spoken at home, is associated with: 1) higher total physical activity levels, and 2) levels of leisure-time physical activity recommended for health benefits in a diverse sample of American Indians. Cross-sectional analysis of 5,207 American Indian adults 18 to 82 years. Participants resided on the Oglala Sioux (n=2,025) and Cheyenne River Sioux (n=1,528) reservations in South Dakota, and the Gila River Indian Community (n=1,654) in Arizona. Bicultural participants in South Dakota, but not Arizona, reported significantly higher total physical activity compared to the English-only group (Pcultures with which they identify are recommended.

  15. A possible new mechanism for the control of miRNA expression in neurons.

    Science.gov (United States)

    Kinjo, Erika Reime; Higa, Guilherme Shigueto Vilar; de Sousa, Erica; Casado, Otávio Augusto Nocera; Damico, Marcio Vinicius; Britto, Luiz Roberto G; Kihara, Alexandre Hiroaki

    2013-10-01

    The control of gene expression by miRNAs has been widely investigated in different species and cell types. Following a probabilistic rather than a deterministic regimen, the action of these short nucleotide sequences on specific genes depends on intracellular concentration, which in turn reflects the balance between biosynthesis and degradation. Recent studies have described the involvement of XRN2, an exoribonuclease, in miRNA degradation and PAPD4, an atypical poly(A) polymerase, in miRNA stability. Herein, we examined the expression of XRN2 and PAPD4 in developing and adult rat hippocampi. Combining bioinformatics and real-time PCR, we demonstrated that XRN2 and PAPD4 expression is regulated by the uncorrelated action of transcription factors, resulting in distinct gene expression profiles during development. Analyses of nuclei position and nestin labeling revealed that both proteins progressively accumulated during neuronal differentiation, and that they are weakly expressed in immature neurons and absent in glial and endothelial cells. Despite the differences in subcellular localization, both genes were concurrently identified within identical neuronal subpopulations, including specific inhibitory interneurons. Thus, we cope with a singular circumstance in biology: an almost complete intersected expression of functional-opposed genes, reinforcing that their antagonistically driven actions on miRNAs "make sense" if simultaneously present at the same cells. Considering that the transcriptome in the nervous system is finely tuned to physiological processes, it was remarkable that miRNA stability-related genes were concurrently identified in neurons that play essential roles in cognitive functions such as memory and learning. In summary, this study reveals a possible new mechanism for the control of miRNA expression. © 2013 Elsevier Inc. All rights reserved.

  16. Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

    Science.gov (United States)

    Hyrina, Anastasia; Olmstead, Andrea D; Steven, Paul; Krajden, Mel; Tam, Edward; Jean, François

    2017-09-01

    In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Bone marrow miR-10a overexpression is associated with genetic events but not affects clinical outcome in acute myeloid leukemia.

    Science.gov (United States)

    Zhang, Ting-Juan; Guo, Hong; Zhou, Jing-Dong; Li, Xi-Xi; Zhang, Wei; Ma, Ji-Chun; Wen, Xiang-Mei; Yao, Xin-Yu; Lin, Jiang; Qian, Jun

    2018-01-01

    Accumulating studies have linked the disruptions of microRNA-10 (miR-10) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML. BM miR-10 expression was examined by real-time quantitative PCR in BM mononuclear cells in 115 de novo AML patients and 45 controls. BM miR-10 (miR-10a/b) expression was significantly up-regulated in AML patients, and was positively correlated with each other. Overexpression of miR-10a was associated with lower percentage of BM blasts, whereas miR-10b overexpression tended to correlate with higher percentage of BM blasts. Importantly, miR-10a overexpression was significantly associated with FAB-M3/t(15;17) subtypes and NPM1 mutation, meanwhile, overexpression of miR-10b was correlated with NPM1 and DNMT3A mutations. However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation. BM miR-10 overexpression is associated with genetic events but not affects clinical outcome in AML. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock bream.

    Science.gov (United States)

    Jo, Ara; Im, Jennifer; Lee, Hee-Eun; Jang, Dongmin; Nam, Gyu-Hwi; Mishra, Anshuman; Kim, Woo-Jin; Kim, Won; Cha, Hee-Jae; Kim, Heui-Soo

    2017-09-10

    MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3' untranslated region (3' UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3' UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Miércoles al cine

    OpenAIRE

    Aguado Franco, Juan Carlos

    2014-01-01

    Se analiza un caso concreto de demanda ante una iniciativa empresarial: los miércoles al cine. Se analiza un caso concreto de demanda ante una iniciativa empresarial: los miércoles al cine. Fundamentos del Análisis Económico

  20. Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study

    DEFF Research Database (Denmark)

    Bork-Jensen, Jette; Thuesen, Anne Cathrine Baun; Bang-Bertelsen, Claus Heiner

    2014-01-01

    Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resist...

  1. Gender-dependent expression of leading and passenger strand of miR-21 and miR-16 in human colorectal cancer and adjacent colonic tissues.

    Science.gov (United States)

    Hasáková, K; Bezakova, J; Vician, M; Reis, R; Zeman, M; Herichova, I

    2017-12-30

    miRNAs are small regulatory RNA molecules involved in posttranscriptional gene silencing. Their biosynthesis results in the formation of duplex consisting of a leading and a passenger strand of mature miRNA. The leading strand exhibits the main activity but recent findings indicate a certain role of the passenger strand as well. Deregulated levels of miRNA were found in many types of cancers including colorectal cancer. miR-21 and miR-16 were indicated as possible markers of colorectal cancer, however, small attention to gender differences in their expression was paid so far. Therefore, the aim of our study was to investigate the expression of miR-21-5p, miR-21-3p, miR-16-5p and miR-16-3p in human colorectal cancer tissue and compare it to the adjacent tissues taken during surgery in men and women separately. Our results showed an up-regulation of all measured miRNAs in tumor tissue compared to adjacent tissues. As expected, tumors and adjacent tissues exhibited a significantly higher expression of leading miRNAs compared to passenger strand of miR-21 and miR-16. The expression of leading and passenger strand of miR-21 and miR-16 positively correlated exhibiting the highest correlation coefficient in the distal tissue. The expression pattern showed gender-dependent differences, with higher levels of miRNA in men than in women. Our findings indicate a gender-related expression pattern of miRNA, which should be considered as an important factor in generating new prognostic or diagnostic biomarkers.

  2. miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker.

    Science.gov (United States)

    Li, Feng; Wang, Feiran; Zhu, Changlai; Wei, Qun; Zhang, Tianyi; Zhou, You Lang

    2018-01-01

    MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC). In this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo. We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC. These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.

  3. Radiosensitizing Effects of Ectopic miR-101 on Non–Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    International Nuclear Information System (INIS)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J.; Wang Ya

    2011-01-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non–small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription–polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein–lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  4. Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J. [Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA (United States); Wang Ya, E-mail: ywang94@emory.edu [Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2011-12-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  5. Long non-coding RNA TUG1 acts as a miR-26a sponge in human glioma cells.

    Science.gov (United States)

    Li, Jun; An, Gang; Zhang, Meng; Ma, Qingfang

    2016-09-02

    Long non-coding RNA taurine upregulated gene 1 (TUG1) acts as an important regulator in cancer pathogenesis; however, its functional mechanism in glioma development remains unclear. This study aims to explore the potential function of TUG1 in glioma by sponging miR-26a. The expression of TUG1, miR-26a, and phosphatase and tensin homolog (PTEN) in 20 paired glioma tissues was detected by quantitative real-time PCR and subjected to correlation analysis. Bioinformatics analysis was performed by using DIANA Tools. Abnormal TUG1 expression was conducted in two glioma cells to analyze its regulation on miR-26a and PTEN using real-time PCR, western blot, and luciferase reporter assay. TUG1 expression was confirmed to be upregulated in glioma tissues, and showed an inverse correlation with downregulated miR-26a. TUG1 could negatively regulate the expression of miR-26a in glioma cells. The bioinformatics prediction revealed putative miR-26a binding sites within TUG1 transcripts. Further experiments demonstrated the positive regulation of TUG1 on the miR-26a target, PTEN, wherein TUG1 could inhibit the negative regulation of miR-26a on PTEN by binding its 3'UTR. Additionally, the expression of PTEN was also upregulated in glioma tissues, showing a positive or negative correlation with TUG1 or miR-26a, respectively. TUG1 could serve as a miR-26a sponge in human glioma cells, contributing to the upregulation of PTEN. This study revealed a new TUG1/miR-26a/PTEN regulatory mechanism and provided a further understanding of the tumor-suppressive role of TUG1 in glioma development. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells.

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    Takehiro Ichikawa

    Full Text Available OBJECTIVE: Trastuzumab has been used for the treatment of HER2-positive breast cancer (BC. However, a subset of BC patients exhibited resistance to trastuzumab therapy. Thus, clarifying the molecular mechanism of trastuzumab treatment will be beneficial to improve the treatment of HER2-positive BC patients. In this study, we identified trastuzumab-responsive microRNAs that are involved in the therapeutic effects of trastuzumab. METHODS AND RESULTS: RNA samples were obtained from HER2-positive (SKBR3 and BT474 and HER2-negetive (MCF7 and MDA-MB-231 cells with and without trastuzumab treatment for 6 days. Next, we conducted a microRNA profiling analysis using these samples to screen those microRNAs that were up- or down-regulated only in HER2-positive cells. This analysis identified miR-26a and miR-30b as trastuzumab-inducible microRNAs. Transfecting miR-26a and miR-30b induced cell growth suppression in the BC cells by 40% and 32%, respectively. A cell cycle analysis showed that these microRNAs induced G1 arrest in HER2-positive BC cells as trastuzumab did. An Annexin-V assay revealed that miR-26a but not miR-30b induced apoptosis in HER2-positive BC cells. Using the prediction algorithms for microRNA targets, we identified cyclin E2 (CCNE2 as a target gene of miR-30b. A luciferase-based reporter assay demonstrated that miR-30b post-transcriptionally reduced 27% (p = 0.005 of the gene expression by interacting with two binding sites in the 3'-UTR of CCNE2. CONCLUSION: In BC cells, trastuzumab modulated the expression of a subset of microRNAs, including miR-26a and miR-30b. The upregulation of miR-30b by trastuzumab may play a biological role in trastuzumab-induced cell growth inhibition by targeting CCNE2.

  7. miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

    Science.gov (United States)

    Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

    2014-10-10

    Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study.

    Science.gov (United States)

    Mazzone, Annette L; Baker, Robert A; McNicholas, Kym; Woodman, Richard J; Michael, Michael Z; Gleadle, Jonathan M

    2018-03-01

    A pilot study to measure and compare blood and urine microRNAs miR-210 and miR-16 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting surgery. Frequent serial blood and urine samples were taken from patients undergoing cardiac surgery with CPB (n = 10) and undergoing off-pump cardiac surgery (n = 5) before, during, and after surgery. Circulating miR-210 and miR-16 levels were determined by relative quantification real-time polymerase chain reaction. Levels of plasma-free haemoglobin (fHb), troponin-T, creatine kinase, and creatinine were measured. Perioperative serum miR-210 and miR-16 were elevated significantly compared to preoperative levels in patients undergoing cardiac surgery with CPB (CPB vs. Pre Op and Rewarm vs. Pre Op; p Octopus on vs. Pre Op); however, the release was less marked when compared to cardiac surgery with CPB. A significant association was observed between both miR-16 and miR-210 and plasma fHb when CPB was used ( r = -.549, p red cell, and renal injury during cardiac surgery.

  9. Koncept oblikovne zasnove multifunkcionalne miške

    OpenAIRE

    Jelenko, Matic

    2016-01-01

    Diplomsko delo opisuje oblikovno zasnovo multifunkcijske miške, katere oblika temelji na združitvi klasične računalniški miške ter 3D miške. Predstavljena je raziskava zgodovine računalniške miške ter proces razvoja od ideje do prototipa. Rezultat je fizični model realne velikosti, narejen z načinom hitre izdelave prototipov. Dodana vrednost je dosežena z implikacijo grafično dekorativne podobe.

  10. Declining Physical Performance Associates with Serum FasL, miR-21, and miR-146a in Aging Sprinters

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    Reeta Kangas

    2017-01-01

    Full Text Available Aging is associated with systemic inflammation and cellular apoptosis accelerating physiological dysfunctions. Whether physically active way of life affects these associations is unclear. This study measured the levels of serum inflammatory and apoptotic molecules, their change over 10 years, and their associations with physical performance in sprint-trained male athletes. HsCRP, cell counts, HGB, FasL, miR-21, and miR-146a were measured cross-sectionally (n=67, 18–90 yrs and serum FasL, miR-21, and miR-146a and their aging-related associations with physical performance were assessed over a 10-year follow-up (n=49, 50–90 yrs. The cross-sectional study showed positive age correlations for neutrophils and negative for lymphocytes, red blood cells, HGB, FasL, and miR-146a. During the 10-year follow-up, FasL decreased (P=0.017 and miR-21 (P<0.001 and miR-146a (P=0.005 levels increased. When combining the molecule levels, aging, and physical performance, FasL associated with countermovement jump and bench press (P<0.001, miR-21 and miR-146a with knee flexion (P=0.023; P<0.001, and bench press (P=0.004; P<0.001 and miR-146a with sprint performance (P<0.001. The studied serum molecules changed in an age-dependent manner and were associated with declining physical performance. They have potential as biomarkers of aging-related processes influencing the development of physiological dysfunctions. Further research is needed focusing on the origins and targets of circulating microRNAs to clarify their function in various tissues with aging.

  11. Large-scale identification and comparative analysis of miRNA expression profile in the respiratory tree of the sea cucumber Apostichopus japonicus during aestivation.

    Science.gov (United States)

    Chen, Muyan; Storey, Kenneth B

    2014-02-01

    The sea cucumber Apostichopus japonicus withstands high water temperatures in the summer by suppressing its metabolic rate and entering a state of aestivation. We hypothesized that changes in the expression of miRNAs could provide important post-transcriptional regulation of gene expression during hypometabolism via control over mRNA translation. The present study analyzed profiles of miRNA expression in the sea cucumber respiratory tree using Solexa deep sequencing technology. We identified 279 sea cucumber miRNAs, including 15 novel miRNAs specific to sea cucumber. Animals sampled during deep aestivation (DA; after at least 15 days of continuous torpor) were compared with animals from a non-aestivation (NA) state (animals that had passed through aestivation and returned to an active state). We identified 30 differentially expressed miRNAs ([RPM (reads per million) >10, |FC| (|fold change|)≥1, FDR (false discovery rate)<0.01]) during aestivation, which were validated by two other miRNA profiling methods: miRNA microarray and real-time PCR. Among the most prominent miRNA species, miR-124, miR-124-3p, miR-79, miR-9 and miR-2010 were significantly over-expressed during deep aestivation compared with non-aestivation animals, suggesting that these miRNAs may play important roles in metabolic rate suppression during aestivation. High-throughput sequencing data and microarray data have been submitted to the GEO database with accession number: 16902695. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis.

    Science.gov (United States)

    Liu, Yanhua; Wang, Xinjing; Jiang, Jing; Cao, Zhihong; Yang, Bingfen; Cheng, Xiaoxing

    2011-05-01

    microRNAs have a critical role in regulating innate and adaptive immunity. To understand whether microRNAs play roles in regulating immune responses to Mycobacterium tuberculosis infection in humans, microRNA expression profiling was performed in PBMCs from pulmonary tuberculosis patients and healthy controls. Analysis of expression profiles showed that expression of 30 microRNAs was significantly altered during active TB as compared with healthy controls, 28 microRNAs were up-regulated and 2 microRNAs down-regulated. miR-144* was one of the microRNAs that were overexpressed in active TB patients. Real-time RT-PCR analysis showed that miR-144* was mainly expressed in T cells. Transfection of T cells with miR-144* precursor demonstrated that miR-144* could inhibit TNF-α and IFN-γ production and T cell proliferation. It is concluded that miR-144* might involve in regulation of anti-TB immunity through modification of cytokine production and cell proliferation of T cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. LncRNA CASC2 inhibited the viability and induced the apoptosis of hepatocellular carcinoma cells through regulating miR-24-3p.

    Science.gov (United States)

    Zeng, Fei; Le, Yi-Guan; Fan, Ji-Chang; Xin, Lin

    2017-11-01

    Background Cancer susceptibility candidate 2 (CASC2), a recently discovered long non-coding RNA (lncRNA), was confirmed to play numerous roles in several human cancers. However, the involvement and concrete mechanism of CASC2 in hepatocellular carcinoma (HCC) still need to be further elucidated. Methods The relative expressions of CASC2 and miR-24-3p in HCC tissue and cell lines were determined by quantitative real-time PCR (qRT-PCR). The effects of CASC2 and miR-24-3p on HCC cells were further assessed via cell viability and apoptosis. In vivo tumorigenesis assay was performed to verify the inhibition effect of CASC2 on the tumor growth and further clarify the important role of miR-24-3p in this mechanism. Results Compared with the paired normal tissues, the relative expression of CASC2 significantly reduced in the HCC tissues, while miR-24-3p as determined by qRT-PCR obviously increased in the HCC tissues. This observation was also found in HCC cell lines. Meanwhile, the expression of CASC2 was negatively related to miR-24-3p expression in the HCC tissues (r = -0.804, p cells, but the up-regulation of miR-24-3p greatly eliminated the CASC2-induced effects. The tumorigenesis of HCC cells was restrained significantly by CASC2 overexpression as shown by decreased tumor volume and growth rate. However, miR-24-3p up-regulation rescued the inhibition of CASC2 on the tumor growth in tumor-bearing mice. Conclusion LncRNA CASC2 inhibited the viability and induced the apoptosis of HCC cells through regulating miR-24-3p. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal cardiomyocytes by repressing GSK-3β protein expression.

    Science.gov (United States)

    Suh, Jong Hui; Choi, Eunmi; Cha, Min-Ji; Song, Byeong-Wook; Ham, Onju; Lee, Se-Yeon; Yoon, Cheesoon; Lee, Chang-Yeon; Park, Jun-Hee; Lee, Sun Hee; Hwang, Ki-Chul

    2012-06-29

    Myocardial ischemia is the major cause of morbidity and mortality due to cardiovascular diseases. This disease is a severe stress condition that causes extensive biochemical changes which trigger cardiac cell death. Stress conditions such as deprivation of glucose and oxygen activate the endoplasmic reticulum in the cytoplasm of cells, including cardiomyocytes, to generate and propagate apoptotic signals in response to these conditions. microRNAs (miRNAs) are a class of small non-coding RNAs that mediate posttranscriptional gene silencing. The miRNAs play important roles in regulating cardiac physiological and pathological events such as hypertrophy, apoptosis, and heart failure. However, the roles of miRNAs in reactive oxygen species (ROS)-mediated injury on cardiomyocytes are uncertain. In this study, we identified at the apoptotic concentration of H(2)O(2), miR-26a expression was increased. To determine the potential roles of miR-26a in H(2)O(2)-mediated cardiac apoptosis, miR-26a expression was regulated by a miR-26a or an anti-miR-26a. Overexpression of miR-26a increased apoptosis as determined by upregulation of Annexin V/PI positive cell population, caspase-3 activity and expression of pro-apoptotic signal molecules, whereas inhibition of miR-26a reduced apoptosis. We identified GSK3B as a direct downstream target of miR-26a. Furthermore, miR-26a attenuated viability and increased caspase-3 activity in normal cardiomyocytes. This study demonstrates that miR-26a promotes ROS-induced apoptosis in cardiomyocytes. Thus, miR-26a affects ROS-mediated gene regulation and cellular injury response. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

    Science.gov (United States)

    Hullinger, Thomas G.; Montgomery, Rusty L.; Seto, Anita G.; Dickinson, Brent A.; Semus, Hillary M.; Lynch, Joshua M.; Dalby, Christina M.; Robinson, Kathryn; Stack, Christianna; Latimer, Paul A.; Hare, Joshua M.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Rationale Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. Objective This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Methods and Results Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Conclusions Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID:22052914

  16. Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R.

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    Lulu Farhana

    Full Text Available MicroRNAs have been implicated in many critical cellular processes including apoptosis. We have previously found that apoptosis in pancreatic cancer cells was induced by adamantyl retinoid-related (ARR molecule 3-Cl-AHPC. Here we report that 3-Cl-AHPC-dependent apoptosis involves regulating a number of microRNAs including miR-150* and miR-630. 3-Cl-AHPC stimulated miR-150* expression and caused decreased expression of c-Myb and IGF-1R in the pancreatic cancer cells. 3-Cl-AHPC-mediated reduction of c-Myb resulted in diminished binding of c-Myb with IGF-1R and Bcl-2 promoters, thereby causing repression of their transcription and protein expression. Over-expression of miR-150* also resulted in diminished levels of c-Myb and Bcl-2 proteins. Furthermore, the addition of the miRNA inhibitor 2'-O-methylated miR-150 blocked 3-Cl-AHPC-mediated increase in miR-150* levels and abrogated loss of c-Myb protein. Knockdown of c-Myb in PANC-1 cells resulted in enhanced apoptosis both in the presence or absence of 3-Cl-AHPC confirming the anti-apoptotic property of c-Myb. Overexpression of miR-630 also induced apoptosis in the pancreatic cancer cells and inhibited target protein IGF-1R mRNA and protein expression. Together these results implicate key roles for miR-150* and miR-630 and their targeting of IGF-1R to promote apoptosis in pancreatic cancer cells.

  17. Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention.

    Science.gov (United States)

    Párrizas, Marcelina; Brugnara, Laura; Esteban, Yaiza; González-Franquesa, Alba; Canivell, Sílvia; Murillo, Serafín; Gordillo-Bastidas, Elizabeth; Cussó, Roser; Cadefau, Joan A; García-Roves, Pablo M; Servitja, Joan-Marc; Novials, Anna

    2015-03-01

    Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies. Here we set to describe the profile of circulating microRNAs (miRNAs) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools. We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance, as well as newly diagnosed diabetic patients. We validated the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention, as well as in a mouse model of glucose intolerance. We identified two miRNAs, miR-192 and miR-193b, whose abundance is significantly increased in the prediabetic state but not in diabetic patients. Strikingly, these miRNAs are also increased in plasma of glucose-intolerant mice. Moreover, circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise, which succeeded in normalizing metabolic parameters. Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans. This circulating miRNA signature for prediabetes could be used as a new diagnostic tool, as well as to monitor response to intervention.

  18. Exosomal miRNAs as biomarkers for prostate cancer

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    Nina Pettersen Hessvik

    2013-03-01

    Full Text Available miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms - associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles or apoptotic bodies or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, noninvasive diagnostic and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.

  19. Detection and analysis of apoptosis- and autophagy-related miRNAs of mouse vascular endothelial cells in chronic intermittent hypoxia model.

    Science.gov (United States)

    Liu, Kai-Xiong; Chen, Gong-Ping; Lin, Ping-Li; Huang, Jian-Chai; Lin, Xin; Qi, Jia-Chao; Lin, Qi-Chang

    2018-01-15

    Endothelial dysfunction is the main pathogenic mechanism of cardiovascular complications induced by obstructive sleep apnea/hyponea syndrome (OSAHS). Chronic intermittent hypoxia (CIH) is the primary factor of OSAHS-associated endothelial dysfunction. The hypoxia inducible factor (HIF) pathway regulates the expression of downstream target genes and mediates cell apoptosis caused by CIH-induced endothelial injury. miRNAs play extensive and important negative regulatory roles in this process at the post-transcriptional level. However, the regulatory mechanism of miRNAs in CIH tissue models remains unclear. The present study established a mouse aortic endothelial cell model of CIH in an attempt to screen out specific miRNAs by using miRNA chip analysis. It was found that 14 miRNAs were differentially expressed. Of them, 6 were significantly different and verified by quantitative real-time PCR (Q-PCR), of which four were up-regulated and two were down-regulated markedly. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, we established signaling networks by GO to predict the target genes of the 6 miRNAs. It was found that the 6 identified miRNAs were apoptosis- or autophagy-related target genes. Down-regulation of miR-193 inhibits CIH induced endothelial injury and apoptosis- or autophagy-related protein expression. In conclusion, our results showed that CIH could induce differential expression of miRNAs, and alteration in the miRNA expression pattern was associated with the expression of apoptosis- or autophagy-related genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis.

    Science.gov (United States)

    Ren, Lin-Lin; Yan, Ting-Ting; Shen, Chao-Qin; Tang, Jia-Yin; Kong, Xuan; Wang, Ying-Chao; Chen, Jinxian; Liu, Qiang; He, Jie; Zhong, Ming; Chen, Hao-Yan; Hong, Jie; Fang, Jing-Yuan

    2018-06-07

    The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.

  1. Institute of American Indian Arts. To Amend the Act of August 27, 1935, to Provide for the Administration, Maintenance, and Operation of the Institute of American Indian Arts by the Indian Arts and Crafts Board. Hearing Before the Committee on Interior and Insular Affairs. House of Representatives, Ninety-Sixth Congress, Second Session on H.R. 6850.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Interior and Insular Affairs.

    The Committee on Interior and Insular Affairs met July 1, 1980, to take testimony on Bill H.R. 6850 which proposed specific statutory authorization for the Institute of American Indian Arts (IAIA), transferred administrative control from the Bureau of Indian Affairs (BIA) to the Indian Arts and Crafts Board (IACB), and reserved the BIA educational…

  2. Dissecting miRNAs in wheat D genome progenitor, Aegilops tauschii

    Directory of Open Access Journals (Sweden)

    Hikmet eBudak

    2016-05-01

    Full Text Available As the post-transcriptional regulators of gene expression, microRNAs or miRNAs comprise an integral part of understanding how genomes function. Although miRNAs have been a major focus of recent efforts, miRNA research is still in its infancy in most plant species. Aegilops tauschii, the D genome progenitor of bread wheat, is a wild diploid grass exhibiting remarkable population diversity. Due to the direct ancestry and the diverse gene pool, A. tauschii is a promising source for bread wheat improvement. In this study, a total of 87 Aegilops miRNA families, including 51 previously unknown, were computationally identified both at the subgenomic level, using flow-sorted A. tauschii 5D chromosome, and at the whole genome level. Predictions at the genomic and subgenomic levels suggested A. tauschii 5D chromosome as rich in pre-miRNAs that are highly associated with Class II DNA transposons. In order to gain insights into miRNA evolution, putative 5D chromosome miRNAs were compared to its modern ortholog, T. aestivum 5D chromosome, revealing that 48 of the 58 A. tauschii 5D miRNAs were conserved in orthologous T. aestivum 5D chromosome. The expression profiles of selected miRNAs (miR167, miR5205, miR5175, miR5523 provided the first experimental evidence for miR5175, miR5205 and miR5523, and revealed differential expressional changes in response to drought in different genetic backgrounds for miR167 and miR5175. Interestingly, while miR5523 coding regions were present and expressed as pre-miR5523 in both T. aestivum and A. tauschii, the expression of mature miR5523 was observed only in A. tauschii under normal conditions, pointing out to an interference at the downstream processing of pre-miR5523 in T. aestivum. Overall, this study expands our knowledge on the miRNA catalogue of Aegilops tauschii, locating a subset specifically to the 5D chromosome, with ample functional and comparative insight which should contribute to and complement efforts to

  3. Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

    Science.gov (United States)

    Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

    2017-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.

  4. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  5. Evolutionary relationships between miRNA genes and their activity.

    Science.gov (United States)

    Zhu, Yan; Skogerbø, Geir; Ning, Qianqian; Wang, Zhen; Li, Biqing; Yang, Shuang; Sun, Hong; Li, Yixue

    2012-12-22

    The emergence of vertebrates is characterized by a strong increase in miRNA families. MicroRNAs interact broadly with many transcripts, and the evolution of such a system is intriguing. However, evolutionary questions concerning the origin of miRNA genes and their subsequent evolution remain unexplained. In order to systematically understand the evolutionary relationship between miRNAs gene and their function, we classified human known miRNAs into eight groups based on their evolutionary ages estimated by maximum parsimony method. New miRNA genes with new functional sequences accumulated more dynamically in vertebrates than that observed in Drosophila. Different levels of evolutionary selection were observed over miRNA gene sequences with different time of origin. Most genic miRNAs differ from their host genes in time of origin, there is no particular relationship between the age of a miRNA and the age of its host genes, genic miRNAs are mostly younger than the corresponding host genes. MicroRNAs originated over different time-scales are often predicted/verified to target the same or overlapping sets of genes, opening the possibility of substantial functional redundancy among miRNAs of different ages. Higher degree of tissue specificity and lower expression level was found in young miRNAs. Our data showed that compared with protein coding genes, miRNA genes are more dynamic in terms of emergence and decay. Evolution patterns are quite different between miRNAs of different ages. MicroRNAs activity is under tight control with well-regulated expression increased and targeting decreased over time. Our work calls attention to the study of miRNA activity with a consideration of their origin time.

  6. Assay reproducibility in clinical studies of plasma miRNA.

    Directory of Open Access Journals (Sweden)

    Jonathan Rice

    Full Text Available There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas and 16 patients without any neoplasm (controls. Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy. We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4% documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively. A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was

  7. Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dinh, Tru-Khang T.; Fendler, Wojciech; Chałubińska-Fendler, Justyna; Acharya, Sanket S.; O’Leary, Colin; Deraska, Peter V.; D’Andrea, Alan D.; Chowdhury, Dipanjan; Kozono, David

    2016-01-01

    Risk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities—such as radiation pneumonitis—during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors. We performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines. miRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation. miR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help

  8. miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer.

    Science.gov (United States)

    Pasqualini, Lorenza; Bu, Huajie; Puhr, Martin; Narisu, Narisu; Rainer, Johannes; Schlick, Bettina; Schäfer, Georg; Angelova, Mihaela; Trajanoski, Zlatko; Börno, Stefan T; Schweiger, Michal R; Fuchsberger, Christian; Klocker, Helmut

    2015-07-01

    The normal prostate as well as early stages and advanced prostate cancer (PCa) require a functional androgen receptor (AR) for growth and survival. The recent discovery of microRNAs (miRNAs) as novel effector molecules of AR disclosed the existence of an intricate network between AR, miRNAs and downstream target genes. In this study DUCaP cells, characterized by high content of wild-type AR and robust AR transcriptional activity, were chosen as the main experimental model. By integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray expression profiling data, miRNAs putatively bound and significantly regulated by AR were identified. A direct AR regulation of miR-22, miR-29a, and miR-17-92 cluster along with their host genes was confirmed. Interestingly, endogenous levels of miR-22 and miR-29a were found to be reduced in PCa cells expressing AR. In primary tumor samples, miR-22 and miR-29a were less abundant in the cancerous tissue compared with the benign counterpart. This specific expression pattern was associated with a differential DNA methylation of the genomic AR binding sites. The identification of laminin gamma 1 (LAMC1) and myeloid cell leukemia 1 (MCL1) as direct targets of miR-22 and miR-29a, respectively, suggested a tumor-suppressive role of these miRNAs. Indeed, transfection of miRNA mimics in PCa cells induced apoptosis and diminished cell migration and viability. Collectively, these data provide additional information regarding the complex regulatory machinery that guides miRNAs activity in PCa, highlighting an important contribution of miRNAs in the AR signaling.

  9. Using Electronic Health Records to Examine Disease Risk in Small Populations: Obesity Among American Indian Children, Wisconsin, 2007-2012.

    Science.gov (United States)

    Tomayko, Emily J; Weinert, Bethany A; Godfrey, Liz; Adams, Alexandra K; Hanrahan, Lawrence P

    2016-02-25

    Tribe-based or reservation-based data consistently show disproportionately high obesity rates among American Indian children, but little is known about the approximately 75% of American Indian children living off-reservation. We examined obesity among American Indian children seeking care off-reservation by using a database of de-identified electronic health records linked to community-level census variables. Data from electronic health records from American Indian children and a reference sample of non-Hispanic white children collected from 2007 through 2012 were abstracted to determine obesity prevalence. Related community-level and individual-level risk factors (eg, economic hardship, demographics) were examined using logistic regression. The obesity rate for American Indian children (n = 1,482) was double the rate among non-Hispanic white children (n = 81,042) (20.0% vs 10.6%, P American Indian children were less likely to have had a well-child visit (55.9% vs 67.1%, P American Indian records (18.3% vs 14.6%, P obesity risk among American Indian children (odds ratio, 1.8; 95% confidence interval, 1.6-2.1) independent of age, sex, economic hardship, insurance status, and geographic designation. An electronic health record data set demonstrated high obesity rates for nonreservation-based American Indian children, rates that had not been previously assessed. This low-cost method may be used for assessing health risk for other understudied populations and to plan and evaluate targeted interventions.

  10. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Jesus Adrian [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico); Alvarez-Salas, Luis Marat, E-mail: lalvarez@cinvestav.mx [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico)

    2011-06-10

    Highlights: {yields} In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. {yields} We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. {yields} We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. {yields} miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. {yields} In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  11. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    International Nuclear Information System (INIS)

    Lopez, Jesus Adrian; Alvarez-Salas, Luis Marat

    2011-01-01

    Highlights: → In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. → We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. → We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. → miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. → In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  12. Colorectal cancer cell-derived exosomes containing miR-10b regulate fibroblast cells via the PI3K/Akt pathway.

    Science.gov (United States)

    Dai, Guangyao; Yao, Xiaoguang; Zhang, Yubin; Gu, Jianbin; Geng, Yunfeng; Xue, Fei; Zhang, Jingcheng

    2018-04-01

    Cancer-associated fibroblasts (CAFs) contribute to the proliferation of colorectal cancer(CRC) cells. However, the mechanism by which CAFs develop in the tumor microenvironment remains unknown. Exosomes may be involved in activating CAFs. Using a miRNA expression profiling array, we determined the miRNA expression profile of secretory exosomes in CRC cells and then identified potential miRNAs with significant differential expression compared to normal cells via enrichment analysis. Predicted targets of candidate miRNAs were then assessed via bioinformatics analysis. Realtime qPCR, western blot, and cell cycle analyses were performed to evaluate the role of candidate exosomal miRNAs. Luciferase reporter assays were applied to confirm whether candidate exosomal miRNAs control target pathway expression. A CRC xenograft mouse model was constructed to evaluate tumor growth in vivo. Exosomes from CRC cells contained significantly higher levels of miR-10b than did exosomes from normal colorectal epithelial cells. Moreover, exosomes containing miR-10b were transferred to fibroblasts. Bioinformatics analysis identified PIK3CA, as a potential target of miR-10b. Luciferase reporter assays confirmed that miR-10b directly inhibited PIK3CA expression. Co-culturing fibroblasts with exosomes containing miR-10b significantly suppressed PIK3CA expression and decreased PI3K/Akt/mTOR pathway activity. Finally, exosomes containing miR-10b reduced fibroblast proliferation but promoted expression of TGF-β and SM α-actin, suggesting that exosomal miR-10b may activate fibroblasts to become CAFs that express myofibroblast markers. These activated fibroblasts were able to promote CRC growth in vitro and in vivo. CRC-derived exosomes actively promote disease progression by modulating surrounding stromal cells, which subsequently acquire features of CAFs. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Individual microRNAs (miRNAs) display distinct mRNA targeting "rules".

    Science.gov (United States)

    Wang, Wang-Xia; Wilfred, Bernard R; Xie, Kevin; Jennings, Mary H; Hu, Yanling Hu; Stromberg, Arnold J; Nelson, Peter T

    2010-01-01

    MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using an assay we validated previously-a "RIP-Chip" experimental design. RIP-Chip data provided a list of mRNAs recruited into the AGO-miRNP in correlation to each miRNA. These experimentally identified miRNA targets were analyzed for complementary six nucleotide "seed" sequences within the transfected miRNAs. We found that miR-124 targets tended to have sequences in the 3'UTR that would be recognized by the 5' seed of miR-124, as described in previous studies. By contrast, miR-107 targets tended to have 'seed' sequences in the mRNA open reading frame, but not the 3' UTR. Further, mRNA targets of miR-128 and miR-320 are less enriched for 6-mer seed sequences in comparison to miR-107 and miR-124. In sum, our data support the importance of the 5' seed in determining binding characteristics for some miRNAs; however, the "binding rules" are complex, and individual miRNAs can have distinct sequence determinants that lead to mRNA targeting.

  14. Investigation of the Application of miR10b and miR135b in the Identification of Semen Stains

    Science.gov (United States)

    Xue, Tianyu; Ma, Xiaoyan; Zhang, Jinxiang; Ou, Xueling; Cheng, Jianding; Sun, Hongyu

    2015-01-01

    To evaluate the identification method using the microRNA markers miR10b and miR135b to distinguish semen stains from menstrual blood, peripheral blood, vaginal fluid and so on body fluid stains. The expression levels of miR10b and miR35b in semen stains and menstrual blood and so on were detected utilizing a real-time quantitative PCR technique with a specific fluorescence-labeled TaqMan probe. RNU6b was used as the internal reference gene; the difference in their expression was analyzed, and the specificity, sensitivity, and detection capability of the techniques were evaluated. The expression of miR10b and miR135b in semen stains was significantly higher than that of other body fluid stains, with a mean value of ΔCт from-6 to-7. However, it ranged from-2 to-4 for other body fluid stains. The initial criteria for judging which semen stains can be identified were determined by analyzing the research results. When the threshold value was set to 0.04, the CT value could be detected in the target genes miR10b, miR135b and in the internal reference gene RNU6b, and CT values are<40, ΔCT[10b-U6]<-5.5, and ΔCT[135b-U6]<-6, respectively, and the semen stain could be identified. The expression levels of miR10b and miR135b are higher in semen with strong tissue specificity; thus, they can be used to differentiate semen stains from other body fluid stains in forensic science. PMID:26355456

  15. Investigation of the Application of miR10b and miR135b in the Identification of Semen Stains.

    Directory of Open Access Journals (Sweden)

    Dayue Tong

    Full Text Available To evaluate the identification method using the microRNA markers miR10b and miR135b to distinguish semen stains from menstrual blood, peripheral blood, vaginal fluid and so on body fluid stains. The expression levels of miR10b and miR35b in semen stains and menstrual blood and so on were detected utilizing a real-time quantitative PCR technique with a specific fluorescence-labeled TaqMan probe. RNU6b was used as the internal reference gene; the difference in their expression was analyzed, and the specificity, sensitivity, and detection capability of the techniques were evaluated. The expression of miR10b and miR135b in semen stains was significantly higher than that of other body fluid stains, with a mean value of ΔCт from-6 to-7. However, it ranged from-2 to-4 for other body fluid stains. The initial criteria for judging which semen stains can be identified were determined by analyzing the research results. When the threshold value was set to 0.04, the CT value could be detected in the target genes miR10b, miR135b and in the internal reference gene RNU6b, and CT values are<40, ΔCT[10b-U6]<-5.5, and ΔCT[135b-U6]<-6, respectively, and the semen stain could be identified. The expression levels of miR10b and miR135b are higher in semen with strong tissue specificity; thus, they can be used to differentiate semen stains from other body fluid stains in forensic science.

  16. Tissue-dependent paired expression of miRNAs

    OpenAIRE

    Ro, Seungil; Park, Chanjae; Young, David; Sanders, Kenton M.; Yan, Wei

    2007-01-01

    It is believed that depending on the thermodynamic stability of the 5′-strand and the 3′-strand in the stem-loop structure of a precursor microRNA (pre-miRNA), cells preferentially select the less stable one (called the miRNA or guide strand) and destroy the other one (called the miRNA* or passenger strand). However, our expression profiling analyses revealed that both strands could be co-accumulated as miRNA pairs in some tissues while being subjected to strand selection in other tissues. Ou...

  17. MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

    Energy Technology Data Exchange (ETDEWEB)

    Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P. [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium); Jacquemin, Patrick, E-mail: patrick.jacquemin@uclouvain.be [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium)

    2010-01-01

    MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

  18. MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

    International Nuclear Information System (INIS)

    Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P.; Jacquemin, Patrick

    2010-01-01

    MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

  19. MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

    Science.gov (United States)

    Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

    2016-11-15

    Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

  20. Regulation of microRNAs miR-30a and miR-143 in cerebral vasculature after experimental subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Müller, Anne Holt; Povlsen, Gro Klitgaard; Edvinsson, Lars

    2015-01-01

    BACKGROUND: microRNAs (miRNAs) are important regulators of translation and have been implicated in the pathogenesis of a number of cardiovascular diseases, including stroke, and suggested as possible prognostic biomarkers. Our aim was to identify miRNAs that are differentially regulated in cerebral...... arteries after subarachnoid hemorrhage (SAH), using a rat injection model of SAH and a qPCR-based screen of 728 rat miRNAs. Additionally, serum was analyzed for a possible spill-over to the circulation of regulated miRNAs from the vessel walls. RESULTS: We identified 482 different miRNAs expressed...

  1. Micromanagement of Immune System: Role of miRNAs in Helminthic Infections.

    Science.gov (United States)

    Arora, Naina; Tripathi, Shweta; Singh, Aloukick K; Mondal, Prosenjit; Mishra, Amit; Prasad, Amit

    2017-01-01

    Helminthic infections fall under neglected tropical diseases, although they inflict severe morbidity to human and causes major economic burden on health care system in many developing countries. There is increased effort to understand their immunopathology in recent days due to their immuno-modulatory capabilities. Immune response is primarily controlled at the transcriptional level, however, microRNA-mediated RNA interference is emerging as important regulatory machinery that works at the translation level. In the past decade, microRNA (miRNA/miR) research has advanced with significant momentum. The result is ever increasing list of curated sequences from a broad panel of organisms including helminths. Several miRNAs had been discovered from trematodes, nematodes and cestodes like let-7, miR155, miR-199, miR-134, miR-223, miR-146, and fhe-mir-125a etc., with potential role in immune modulation. These miRs had been associated with TGF-β, MAPK, Toll-like receptor, PI3K/AKT signaling pathways and insulin growth factor regulation. Thus, controlling the immune cells development, survival, proliferation and death. Apart from micromanagement of immune system, they also express certain unique miRNA also like cis- miR-001, cis- miR-2, cis- miR-6, cis- miR-10, cis- miR-18, cis- miR-19, trs-mir-0001, fhe-miR-01, fhe-miR-07, fhe-miR-08, egr-miR-4988, egr-miR-4989 etc. The specific role played by most of these species specific unique miRs are yet to be discovered. However, these newly discovered miRNAs might serve as novel targets for therapeutic intervention or biomarkers for parasitic infections.

  2. Barriers and Facilitators to Being Physically Active on a Rural U.S. Northern Plains American Indian Reservation

    Directory of Open Access Journals (Sweden)

    Lisa Jahns

    2014-11-01

    Full Text Available The objective of the present study was to identify barriers to and facilitators of physical activity among American Indian adults living on a rural, U.S. Northern Plains reservation using the nominal group technique (NGT. NGT is a method of data generation and interpretation that combines aspects of qualitative (free generation of responses and quantitative (systematic ranking of responses methodologies. Adults participated in one of two NGT sessions asking about either barriers to (n = 6, or facilitators of (n = 5, being physically active. Participants nominated and ranked 21 barriers and 18 facilitators. Barriers indicated lack of knowledge of how to fit physical activity into a daily schedule, work, caring for family members, and prioritizing sedentary pursuits. Other responses included environmental barriers such as lack of access and transportation to a gym, unsafe walking conditions, and inclement weather. Facilitators to following recommendations included knowledge of health benefits of physical activity and the perception of physical activity as enjoyable, including feeling good when working out. Environmental facilitators included being outdoors walking and biking as well as parks and exercise facilities. Responses provided direction for locally designed community-based programs to promote facilitators and decrease barriers to individual’s engagement in physical activity.

  3. GPC1 Regulated by miR-96-5p, Rather than miR-182-5p, in Inhibition of Pancreatic Carcinoma Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Chunlong Li

    2014-04-01

    Full Text Available To determine the relationships between miR-96-5p/-182-5p and GPC1 in pancreatic cancer (PC, we conducted the population and in vitro studies. We followed 38 pancreatic cancer patients, measured and compared the expression of miR-96-5p/-182-5p, GPC1, characteristics and patients’ survival time of different miR-96-5p/-182-5p expression levels in PC tissues. In an in vitro study, we investigated the proliferation, cycle and apotosis in cells transfected with mimics/inhibitors of the two miRNAs, and determine their effects on GPC1 by dual-luciferase assay. In the follow-up study, we found that the expressions of miR-96-5p/-182-5p were lower/higher in PC tissues; patients with lower/higher levels of miR-96-5p/-182-5p suffered poorer characteristics and decreased survival time. In the in vitro study, the expressions of miR-96-5p/-182-5p were different in cells. Proliferation of cells transfected with miR-96-5p mimics/inhibitors was lower/higher in Panc-1/BxPC-3; when transfected with miR-182-5p mimics/inhibitors, proliferation of cells were higher/lower in AsPC-1/Panc-1. In a cell cycle study, panc-1 cells transfected with miR-96-5p mimics was arrested at G0/G1; BxPC-3 cells transfected with miR-96-5p inhibitors showed a significantly decrease at G0/G1; AsPC-1 cells transfected with miR-182-5p mimics was arrested at S; Panc-1 cells transfected with miR-182-5p inhibitors showed a decrease at S. MiR-96-5p mimics increased the apoptosis rate in Panc-1 cells, and its inhibitors decreased the apoptosis rate in BxPC-3. Dual luciferase assay revealed that GPC1 was regulated by miR-96-5p, not -182-5p. We found that miR-96-5p/-182-5p as good markers for PC; miR-96-5p, rather than -182-5p, inhibits GPC1 to suppress proliferation of PC cells.

  4. Surface-water quality, Oneida Reservation and vicinity, Wisconsin, 1997-98

    Science.gov (United States)

    Schmidt, Morgan A.; Scudder, Barbara C.; Richards, Kevin D.

    2000-01-01

    Streamwater samples were collected at 19 sites in the vicinity of the Oneida Tribe of Indians of Wisconsin Reservation. Samples were collected during 5 sampling periods in 1997-98. Field measurements were made and samples were analyzed for nutrients, suspended sediment, major ions, and pesticides.

  5. miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

    Science.gov (United States)

    Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

    2017-08-08

    Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

  6. Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling.

    Science.gov (United States)

    Fu, Wei-Ming; Zhu, Xiao; Wang, Wei-Mao; Lu, Ying-Fei; Hu, Bao-Guang; Wang, Hua; Liang, Wei-Cheng; Wang, Shan-Shan; Ko, Chun-Hay; Waye, Mary Miu-Yee; Kung, Hsiang-Fu; Li, Gang; Zhang, Jin-Fang

    2015-10-01

    Long non-coding RNA Hotair has been considered as a pro-oncogene in multiple cancers. Although there is emerging evidence that reveals its biological function and the association with clinical prognosis, the precise mechanism remains largely elusive. We investigated the function and mechanism of Hotair in hepatocellular carcinoma (HCC) cell models and a xenograft mouse model. The regulatory network between miR-218 and Hotair was elucidated by RNA immunoprecipitation and luciferase reporter assays. Finally, the correlation between Hotair, miR-218 and the target gene Bmi-1 were evaluated in 52 paired HCC specimens. In this study, we reported that Hotair negatively regulated miR-218 expression in HCC, which might be mediated through an EZH2-targeting-miR-218-2 promoter regulatory axis. Further investigation revealed that Hotair knockdown dramatically inhibited cell viability and induced G1-phase arrest in vitro and suppressed tumorigenicity in vivo by promoting miR-218 expression. Oncogene Bmi-1 was shown to be a functional target of miR-218, and the main downstream targets signaling, P16(Ink4a) and P14(ARF), were activated in Hotair-suppressed tumorigenesis. In primary human HCC specimens, Hotair and Bmi-1 were concordantly upregulated whereas miR-218 was downregulated in these tissues. Furthermore, Hotair was inversely associated with miR-218 expression and positively correlated with Bmi-1 expression in these clinical tissues. Hotair silence activates P16(Ink4a) and P14(ARF) signaling by enhancing miR-218 expression and suppressing Bmi-1 expression, resulting in the suppression of tumorigenesis in HCC. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.

    Science.gov (United States)

    Liu, Yi; Luo, Fei; Wang, Bairu; Li, Huiqiao; Xu, Yuan; Liu, Xinlu; Shi, Le; Lu, Xiaolin; Xu, Wenchao; Lu, Lu; Qin, Yu; Xiang, Quanyong; Liu, Qizhan

    2016-01-01

    Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells.

    Science.gov (United States)

    Lin, Xian-Zi; Luo, Jun; Zhang, Li-Ping; Wang, Wei; Shi, Heng-Bo; Zhu, Jiang-Jiang

    2013-05-25

    MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides, participate in various biological metabolic processes. miR-27a is a miRNA that is known to regulate fat synthesis and differentiation in preadipocyte cells. However, little is known regarding the role that miR-27a plays in regulating goat milk fat synthesis. In this study, we determined the miR-27a expression profile in goat mammary gland and found that miR-27a expression was correlated with the lactation cycle. Additionally, prolactin promoted miR-27a expression in goat mammary gland epithelial cells. Further functional analysis showed that over-expression of miR-27a down-regulated triglyceride accumulation and decreased the ratio of unsaturated/saturated fatty acid in mammary gland epithelial cells. miR-27a also significantly affected mRNA expression related to milk fat metabolism. Specifically, over-expression of miR-27a reduced gene mRNA expression associated with triglyceride synthesis by suppressing PPARγ protein levels. This study provides the first experimental evidence that miR-27a regulates triglyceride synthesis in goat mammary gland epithelial cells and improves our understanding about the importance of miRNAs in milk fat synthesis. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  9. MiR-143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells.

    Science.gov (United States)

    Liu, Jing; Qu, Cheng-Bin; Xue, Yi-Xue; Li, Zhen; Wang, Ping; Liu, Yun-hui

    Therapeutic applications of microRNAs (miRNAs) in chemotherapy were confirmed to be valuable, but there is rare to identify their specific roles and functions in shikonin treatment toward tumors. Here, for the first time, we reported that miR-143 played a critical role in the antitumor activity of shikonin in glioblastoma stem cells (GSCs). The results showed that the expression of miR-143 was downregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly enhanced the inhibitory effect of shikonin toward GSCs on cell viability. Besides, miR-143 overexpression caused a significant increase in the apoptotic fraction and made apoptosis occur earlier. Further investigation identified that BAG3, an apoptotic regulator, was a functional target of miR-143 in shikonin treated GSCs. The expression of BAG3 was upregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly reversed the high expression of BAG3 in shikonin treated GSCs. Moreover, it was confirmed that the enhanced cytotoxicity of shikonin by miR-143 overexpression was reversed by BAG3 overexpression both in vitro and in vivo, suggesting that the enhanced tumor suppressive effects by miR-143 overexpression was at least partly through the regulation of BAG3. Taken together, for the first time, our results demonstrate that miR-143 could enhance the antitumor activity of shikonin toward GSCs through reducing BAG3 expression, which may provide a novel therapeutic strategy for enhancing the treatment efficacy of shikonin toward GSCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    International Nuclear Information System (INIS)

    Kim, Byeong-Moo; Choi, Michael Y.

    2012-01-01

    Highlights: ► Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. ► miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. ► miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. ► miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. ► miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3′-untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  11. miRNA-205 affects infiltration and metastasis of breast cancer

    International Nuclear Information System (INIS)

    Wang, Zhouquan; Liao, Hehe; Deng, Zhiping; Yang, Po; Du, Ning; Zhanng, Yunfeng; Ren, Hong

    2013-01-01

    Highlights: •We detected expression of miR-205 in breast cancer cell lines and tissue samples. •We suggest miR-205 is downregulated in human breast cancer tissues and MCF7 cells. •We suggest the lower expression of miR-205 play a role in breast cancer onset. •These data suggest that miR-205 directly targets HER3 in human breast cancer. -- Abstract: Background: An increasing number of studies have shown that miRNAs are commonly deregulated in human malignancies, but little is known about the function of miRNA-205 (miR-205) in human breast cancer. The present study investigated the influence of miR-205 on breast cancer malignancy. Methods: The expression level of miR-205 in the MCF7 breast cancer cell line was determined by quantitative (q)RT-PCR. We then analyzed the expression of miR-205 in breast cancer and paired non-tumor tissues. Finally, the roles of miR-205 in regulating tumor proliferation, apoptosis, migration, and target gene expression were studied by MTT assay, flow cytometry, qRT-PCR, Western blotting and luciferase assay. Results: miR-205 was downregulated in breast cancer cells or tissues compared with normal breast cell lines or non-tumor tissues. Overexpression of miR-205 reduced the growth and colony-formation capacity of MCF7 cells by inducing apoptosis. Overexpression of miR-205 inhibited MCF7 cell migration and invasiveness. By bioinformation analysis, miR-205 was predicted to bind to the 3′ untranslated regions of human epidermal growth factor receptor (HER)3 mRNA, and upregulation of miR-205 reduced HER3 protein expression. Conclusion: miR-205 is a tumor suppressor in human breast cancer by post-transcriptional inhibition of HER3 expression

  12. Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5

    Directory of Open Access Journals (Sweden)

    Gökçe Güllü

    2015-03-01

    Full Text Available The functional role of IGFBP5 in breast cancer is complicated. Experimental and bioinformatics studies have shown that IGFBP5 is targeted by miR-140-5p and miR-193b, although this has not yet been proven in clinical samples. The aim of this study was to evaluate the expression of miR-140-5p and miR-193b in breast cancer and adjacent normal tissue and assess its correlation with IGFBP5 and the clinicopathological characteristics of the tumors. IGFBP5 protein expression was analyzed immunohistochemically and IGFBP5, miR-140 and miR-193b mRNA expression levels were analyzed with real-time RT-PCR. Tumor tissue had higher miR-140-5p expression than adjacent normal tissue (p = 0.015. Samples with no immunohistochemical staining for IGFBP5 showed increased miR-140-5p expression (p = 0.009. miR-140-5p expression was elevated in invasive ductal carcinomas (p = 0.002, whereas basal-like tumors had decreased expression of miR-140-5p compared to other tumors (p = 0.008. Lymph node-positive samples showed an approximately 13-fold increase in miR-140-5p expression compared to lymph node-negative tissue (p = 0.049. These findings suggest that miR-140-5p, but not miR-193b, could be an important determinant of IGFBP5 expression and clinical phenotype in breast cancer patients. Further studies are needed to clarify the expressional regulation of IGFBP5 by miR-140-5p.

  13. CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

    Science.gov (United States)

    Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

    2018-02-23

    Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

  14. IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer.

    Science.gov (United States)

    Mal, Chittabrata; Aftabuddin, Md; Kundu, Sudip

    2018-03-16

    Growing evidences suggest that microRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. It has been previously reported that plant/food-derived miRNAs are highly enriched in human serum or serum from phytophagous animals, and they are responsible for regulating mammalian gene expression. Thus, miRNAs could function as active signaling molecules, which carry information across distinct species or even kingdoms. However, the mode of miRNA shuttling among various organisms is still a mystery to unravel. The intra and inter kingdom miRNA transfer has boosted up the hypothesis about the potential impact of plant or animal miRNAs on each other. To our knowledge, the software for analyzing cross-kingdom miRNA-targets is lacking. We have developed a web-tool "IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer" utilizing a database; the data of which have been collected from another web server. Here, user can analyze the targeting potential of (i) plant miRNAs on animal UTRs (Untranslated regions), and vice versa (i.e., inter kingdom), (ii) plant miRNAs on plant UTRs and animal miRNAs on animal UTRs (i.e., intra kingdom). Further, user can analyze (i) miRNAs to targets, (ii) targets to miRNAs, and (iii) miRNA sets targeting sets of targets. For a wide variety of animal and plant species, IIKmTA can identify the miRNA binding sites in the probable target UTRs. Moreover, GC% and AU% of miRNAs will be calculated. All the results can be saved as .csv file. Recent researches identified miRNAs in plants and human secretions and their role in regulating the human genes. Such findings indicate the therapeutic role of secretory miRNAs of such plants which exhibits medicinal value and in near future many diseases may be treated by consumption of these plant miRNAs through food. Using our newly developed database and analyzing tool, one can easily determine the different relationships between miRNAs and their targets across kingdoms

  15. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Smile characterization by U.S. white, U.S. Asian Indian, and Indian populations.

    Science.gov (United States)

    Sharma, Neeru; Rosenstiel, Stephen F; Fields, Henry W; Beck, F Mike

    2012-05-01

    .S. whites. Differences attributed to assimilation were demonstrated between U.S. Asian Indians and Asian Indians. Differences between U.S. Asian Indians and U.S. whites can be instructive and demonstrate the relative power of ethnicity and assimilation. A difference between these groups shows the power of ethnicity and no difference between these groups shows the power of assimilation. The ratings of the Asian Indians and the U.S. whites showed a clinically significant difference for Ideal Buccal Corridor and Maximum Smile Arc. There were no significant differences between the U.S. Asian Indians and Asian Indians. There were clinically significant differences between the U.S. Asian Indians and U.S. whites only for Ideal Buccal Corridor. Ethnicity had a significant effect on the esthetic choices for Buccal Corridor and Smile Arc. There is no conclusive evidence for assimilation. Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  17. Indian Reservations

    Data.gov (United States)

    Department of Homeland Security — The TIGER/Line shapefiles and related database files (.dbf) are an extract of selected geographic and cartographic information from the U.S. Census Bureau's Master...

  18. Inactivation of p53 in pterygium influence miR-200a expression resulting in ZEB1/ZEB2 up-regulation and EMT processing.

    Science.gov (United States)

    Wu, Chueh-Wei; Peng, Mei-Ling; Yeh, Ken-Tu; Tsai, Yi-Yu; Chiang, Chun-Chi; Cheng, Ya-Wen

    2016-05-01

    Loss of p53 function has been linked to progression of pterygium. MiR-200a is known to be controlled by p53. Here, we hypothesize that expression of miR-200a and downstream ZEB1/ZEB2 genes are regulated epithelial-mesenchymal transition (EMT) involved in the pathogenesis and recurrence of pterygium. For this study, 120 primary pterygial samples were collected. Immunohistochemistry and real-time RT-PCR were performed to determine the expression of p53, p53 down-stream EMT associated protein and miR-200a. The molecular correlation of p53, miR-200a and downstream genes were confirmed using primary pterygium cells (PECs). Expression of miR-200a in pterygium tissues was significantly lower than in conjunctiva controls (p = 0.015). Up-regulated miR-200a levels were positively correlated with and p53 protein expression (p influence miR-200a, resulting in ZEB1/ZEB2 up-regulation and EMT processing of pterygium. Therefore, we suggest that expression of miR-200a play an important role in EMT processing and recurrence of pterygium. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Towards an understanding of miRNA regulation

    DEFF Research Database (Denmark)

    Jensen, Trine Ilsø

    miRNAs are well-known regulators of gene expression. They function post-transcriptionally by binding to complementary sites within the 3´UTR of target mRNAs, which mediates translational repression and destabilization. However, miRNA expression itself is also subjected to regulation. Here, we...... report a new method to investigate and potentially characterize the pri-miRNA transcript. Overexpression of a transdominant Drosha mutant, which is unable to cleave its substrate, enables stabilization of the pri-miRNA transcript. Drosha mutant immunoprecipitation from the nuclear compartment...... is performed followed by high-throughput sequencing (nuclear Drosha Mt2 RIPseq). This method allows for the detection of global pri-miRNA signature and also provides a method to potentially identify new Drosha substrates. Furthermore, data on the identification of a novel endogenous circular RNA sponge (ciRS-7...

  20. "Now the Work Begins": Gender Equality in Sámi Politics

    OpenAIRE

    Pedersen, Linn-Marie Lillehaug

    2014-01-01

    This study examines gender equality in Sámi politics after 2005, the year the Sámi Parliament achieved balanced gender representation. The project seeks to answer the question: Within the context of Sámi politics, how is gender equality represented and addressed? To answer this question, the study is based on official documents by the Sámi Parliament and the women’s organization Sámi NissonForum, as well as six semi-structured interviews with Sámi politicians and Sámi women’s activists. Quali...

  1. Weaving dreamcatchers: mothering among American Indian women who were teen mothers.

    Science.gov (United States)

    Palacios, Janelle F; Strickland, Carolyn J; Chesla, Catherine A; Kennedy, Holly P; Portillo, Carmen J

    2014-01-01

    The aim of this study was to explore the mothering experience and practice among reservation-based adult American Indian women who had been adolescent mothers. Adolescent American Indian women are at an elevated risk for teen pregnancy and poor maternal/child outcomes. Identifying mothering practices among this population may help guide intervention development that will improve health outcomes. A collaborative orientation to community-based participatory research approach. Employing interpretive phenomenology, 30 adult American Indian women who resided on a Northwestern reservation were recruited. In-depth, face-to-face and telephone interviews were conducted between 2007-2008. Women shared their mothering experience and practice, which encompassed a lifespan perspective grounded in their American Indian cultural tradition. Four themes were identified as follows: mother hen, interrupted mothering and second chances, breaking cycles and mothering a community. Mothering originated in childhood, extended across their lifespan and moved beyond mothering their biological offspring. These findings challenge the Western construct of mothering and charge nurses to seek culturally sensitive interventions that reinforce positive mothering practices and identify when additional mothering support is needed across a woman's lifespan. © 2013 John Wiley & Sons Ltd.

  2. Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo

    Directory of Open Access Journals (Sweden)

    Thomas Conrad

    2014-10-01

    Full Text Available In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

  3. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

    Science.gov (United States)

    Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

    2014-02-01

    Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

  4. miR-22 regulates cell invasion, migration and proliferation in vitro through inhibiting CD147 expression in tongue squamous cell carcinoma.

    Science.gov (United States)

    Qiu, Kaifeng; Huang, Zixian; Huang, Zhiquan; He, Zhichao; You, Siping

    2016-06-01

    Tongue squamous cell carcinoma (TSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) in China, and its survival rate remains unsatisfactory. miR-22 has been identified as a tumor suppressor in many human cancers, and high expression of CD147 occurs in many tumors. The aim of the present study was to investigate the expression and function of miR-22 in TSCC and its relationship with the expression of CD147. TCA8113 cells were transiently transfected with a miR-22 mimic/inhibitor. Subsequently, a validation with Real-time RT-PCR was performed to analyze the miR-22 expression level, and a CCK-8 proliferation assay and transwell migration and invasion assays were carried out. Cotransfections using As-miR-22/si-CD147 mRNA or a miR-22/CD147 overexpression vector were applied, and we investigated the biological effects on cotranscribed TCA8113 cells. qRT-PCR confirmed that miR-22 or As-miR-22 were successfully transfected into TCA8113 cells. Suppressing miR-22 resulted in a promotion of cell proliferation and motility and an up-regulation of CD147 in TCA8113 cells in vitro. In contrast, increasing miR-22 inhibited cell proliferation and motility and down-regulated CD147. Furthermore, the reduction or overexpression of CD147 can reverse the promoting or suppressive effects of miR-22, respectively. The down-expression of miR-22 can regulate cell growth and motility in TSCC cells, which indicates that miR-22 acts as a tumor suppressor in TSCC. Additionally, CD147 is subsequently up-regulated when miR-22 inhibited. Taken together, the findings of this research defined a novel relationship between the down-regulation of miR-22 and the up-regulation of CD147 and demonstrated that CD147 is a downstream factor of miR-22. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. miRMaid: a unified programming interface for microRNA data resources

    DEFF Research Database (Denmark)

    Jacobsen, Anders; Krogh, Anders; Kauppinen, Sakari

    2010-01-01

    miRBase data as inter-connected web services. Third-party miRNA data resources can be modularly integrated as miRMaid plugins or they can loosely couple with miRMaid as individual entities in the World Wide Web. miRMaid is available as a public web service but is also easily installed as a local...... here as miRMaid, with the goal of integrating miRNA data resources in a uniform web service interface that can be accessed and queried by researchers and, most importantly, by computers. miRMaid is built around data from miRBase and is designed to follow the official miRBase data releases. It exposes...

  6. GIMDA: Graphlet interaction-based MiRNA-disease association prediction.

    Science.gov (United States)

    Chen, Xing; Guan, Na-Na; Li, Jian-Qiang; Yan, Gui-Ying

    2018-03-01

    MicroRNAs (miRNAs) have been confirmed to be closely related to various human complex diseases by many experimental studies. It is necessary and valuable to develop powerful and effective computational models to predict potential associations between miRNAs and diseases. In this work, we presented a prediction model of Graphlet Interaction for MiRNA-Disease Association prediction (GIMDA) by integrating the disease semantic similarity, miRNA functional similarity, Gaussian interaction profile kernel similarity and the experimentally confirmed miRNA-disease associations. The related score of a miRNA to a disease was calculated by measuring the graphlet interactions between two miRNAs or two diseases. The novelty of GIMDA lies in that we used graphlet interaction to analyse the complex relationships between two nodes in a graph. The AUCs of GIMDA in global and local leave-one-out cross-validation (LOOCV) turned out to be 0.9006 and 0.8455, respectively. The average result of five-fold cross-validation reached to 0.8927 ± 0.0012. In case study for colon neoplasms, kidney neoplasms and prostate neoplasms based on the database of HMDD V2.0, 45, 45, 41 of the top 50 potential miRNAs predicted by GIMDA were validated by dbDEMC and miR2Disease. Additionally, in the case study of new diseases without any known associated miRNAs and the case study of predicting potential miRNA-disease associations using HMDD V1.0, there were also high percentages of top 50 miRNAs verified by the experimental literatures. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. 25 CFR 227.14 - Government reserves right to purchase oil and gas.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Government reserves right to purchase oil and gas. 227.14... § 227.14 Government reserves right to purchase oil and gas. In time of war or other public emergency any... posted market price on the date of sale all or any part of the minerals produced under any lease. Rents...

  8. Czesław Miłosz “On Oneself as Another”: Miłosz - Ricoeur

    Directory of Open Access Journals (Sweden)

    Agnieszka Rydz

    2012-01-01

    Full Text Available The article is thematically related to the fundamental essay by the French hermeneutic philosopher, On Oneself as Another, which discussed with reference to Miłosz’s later writings (poetry and essays. The autobiographical quality of Miłosz’s expression is discussed through the concept of “otherness” as presented by Ricoeur. The discussion is con­ducted in the framework of triple relation of a subjective “I”: to one’s body, to the Other, and to one’s conscience. Miłosz, in his later works, responds to the ailings of the body with understanding, or even a sort of tenderness. Similar emotions are evoked by his contact with the Other, embodied by his ancestors and contemporaries. The responsibility for another person, however, and the communion with fellow people, are related, in his work, with the category of conscience. An attempt to narrate “oneself as another” allowed the Polish poet to reduce the seemingly irremovable rift between an artist and “the human family”; that rift was for Miłosz a troublesome legacy of modernism.

  9. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Characterization of miRNomes in Acute and Chronic Myeloid

    Directory of Open Access Journals (Sweden)

    Qian Xiong

    2014-04-01

    Full Text Available Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

  11. The tumor suppressor role of miR-124 in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Shuo Geng

    Full Text Available MicroRNAs have crucial roles in development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-124 was down-regulated in many cancers; however, the role of miR-124 in osteosarcoma development is unknown. In this study, we demonstrate that expression of miR-124 is significantly downregulated in osteosarcoma tissues and cell lines, compared to the adjacent tissues. The expression of miR-124 in the metastases osteosarcoma tissues was lower than that in non- metastases tissues. We identified and confirmed Rac1 as a novel, direct target of miR-124 using prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed Rac1 protein expression and attenuated cell proliferation, migration, and invasion and induced apoptosis in MG-63 and U2OS in vitro. Moreover, overexpression of Rac1 in miR-124-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion caused by miR-124. Therefore, our results demonstrate that miR-124 is a tumor suppressor miRNA and suggest that this miRNA could be a potential target for the treatment of osteosarcoma in future.

  12. Asian Indians in America: The influence of values and culture on mental health.

    Science.gov (United States)

    Chandra, Rohit M; Arora, Lily; Mehta, Urvakhsh M; Asnaani, Anu; Radhakrishnan, Rajiv

    2016-08-01

    Asian Indians represent a significant portion of the largest growing race of Asians in the past decade in the United States. This selective review examines major cultural themes related to first- and second-generation Asian Indians living in the United States as they impact psychological and psychiatric dysfunction in this population. Specifically, we review the impact of Asian Indian culture on mental health, discuss the impact of acculturation and ethnic identity development on the mental health of Indian-Americans, and focus on typical mental health problems of Asian Indian adolescents, women and elderly in America. Finally, we provide a brief overview of empirically-supported treatment approaches and cultural considerations for additional treatments relevant to this population. This review is intended to provide an important foundation for more systematic empirically-driven investigation into better understanding how Asian Indian cultural themes impact mental health for Indian-Americans, and how to develop effective treatments for these issues in this cultural group. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism

    Directory of Open Access Journals (Sweden)

    Marco De Martino

    2017-11-01

    Full Text Available Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression.

  14. Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.

    Science.gov (United States)

    Müller-Deile, Janina; Dannenberg, Jan; Schroder, Patricia; Lin, Meei-Hua; Miner, Jeffrey H; Chen, Rongjun; Bräsen, Jan-Hinrich; Thum, Thomas; Nyström, Jenny; Staggs, Lynne Beverly; Haller, Hermann; Fiedler, Jan; Lorenzen, Johan M; Schiffer, Mario

    2017-10-01

    The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ying-fei [Institute Guangzhou of Advanced Technology, Chinese Academy of Sciences, Guangzhou (China); Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); Zhang, Li [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong (China); Waye, Mary Miu Yee [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Fu, Wei-ming, E-mail: wm.fu@giat.ac.cn [Institute Guangzhou of Advanced Technology, Chinese Academy of Sciences, Guangzhou (China); School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Jin-fang, E-mail: zhangjf06@cuhk.edu.hk [Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen (China)

    2015-05-15

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.

  16. MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

    International Nuclear Information System (INIS)

    Lu, Ying-fei; Zhang, Li; Waye, Mary Miu Yee; Fu, Wei-ming; Zhang, Jin-fang

    2015-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways

  17. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byeong-Moo [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Choi, Michael Y., E-mail: mchoi@partners.org [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Harvard Stem Cell Institute, Boston, MA 02114 (United States)

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  18. Evaluation of circulating miRNAs during late pregnancy in the mare.

    Directory of Open Access Journals (Sweden)

    Shavahn C Loux

    Full Text Available MicroRNAs (miRNAs are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss; however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation and post-partum, as well as from non-pregnant (diestrous mares. In total, we evaluated a panel of 178 miRNAs using qPCR, eventually identifying five miRNAs of interest. One miRNA (miR-374b was differentially regulated through late gestation and four miRNAs (miR-454, miR-133b, miR-486-5p and miR-204b were differentially regulated between the pregnant and non-pregnant samples. We were able to identify putative targets for the differentially regulated miRNAs using two separate target prediction programs, miRDB and Ingenuity Pathway Analysis. The targets for the miRNAs differentially regulated during pregnancy were predicted to be involved in signaling pathways such as the STAT3 pathway and PI3/AKT signaling pathway, as well as more endocrine-based pathways, including the GnRH, prolactin and insulin signaling pathways. In summary, this study provides novel information about the changes occurring in circulating miRNAs during normal pregnancy, as well as attempting to predict the biological effects induced by these miRNAs.

  19. Exosomes as miRNA Carriers: Formation–Function–Future

    Science.gov (United States)

    Yu, Xiaojie; Odenthal, Margarete; Fries, Jochen W. U.

    2016-01-01

    Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine. PMID:27918449

  20. Exosomes as miRNA Carriers: Formation–Function–Future

    Directory of Open Access Journals (Sweden)

    Xiaojie Yu

    2016-12-01

    Full Text Available Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs. miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.

  1. dPORE-miRNA: Polymorphic regulation of microRNA genes

    KAUST Repository

    Schmeier, Sebastian; Schaefer, Ulf; MacPherson, Cameron R.; Bajic, Vladimir B.

    2011-01-01

    Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.

  2. dPORE-miRNA: Polymorphic regulation of microRNA genes

    KAUST Repository

    Schmeier, Sebastian

    2011-02-04

    Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.

  3. Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations

    DEFF Research Database (Denmark)

    Zedan, Ahmed Hussein; Blavnsfeldt, Søren Garm; Hansen, Torben Frøstrup

    2017-01-01

    ).RESULTS: Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126) were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH), and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0......-free survival (p = 0.016).CONCLUSION: The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra...

  4. Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations

    DEFF Research Database (Denmark)

    Zedan, Ahmed Hussein; Blavnsfeldt, Søren Garm; Hansen, Torben Frøstrup

    2017-01-01

    ). RESULTS: Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126) were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH), and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0......-free survival (p = 0.016). CONCLUSION: The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra...

  5. Protein-driven inference of miRNA-disease associations

    DEFF Research Database (Denmark)

    Mørk, Søren; Pletscher-Frankild, Sune; Palleja, Albert

    2014-01-01

    MicroRNAs (miRNAs) are a highly abundant class of non-coding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA-disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction...

  6. Convection-enhanced delivery of an anti-miR is well-tolerated, preserves anti-miR stability and causes efficient target de-repression

    DEFF Research Database (Denmark)

    Halle, Bo; Marcusson, Eric G; Aaberg-Jessen, Charlotte

    2016-01-01

    Over-expressed microRNAs (miRs) are promising new targets in glioblastoma (GBM) therapy. Inhibition of over-expressed miRs has been shown to diminish GBM proliferation, invasion and angiogenesis, indicating a significant therapeutic potential. However, the methods utilized for miR inhibition have...... had low translational potential. In clinical trials convection-enhanced delivery (CED) has been applied for local delivery of compounds in the brain. The aim of this study was to determine if safe and efficient miR inhibition was possible by CED of an anti-miR. We used a highly invasive GBM orthotopic...

  7. Registered indians and tobacco taxation: a culturally-appropriate strategy?

    Science.gov (United States)

    Wardman, A E Dennis; Khan, Nadia A

    2005-01-01

    Taxation of tobacco is a widely-used strategy that prompts smoking cessation among adults and reduces cigarette consumption among continuing smokers. Registered Indian tobacco use prevalence is at least double that of the rest of Canadians and is in part due to the lower cost of tobacco products purchased on reserve by Registered Indians (RIs) as they are tax exempt. Although registered Indian communities have the ability to collect tax on tobacco products and direct the use of these revenues, this strategy is rarely utilized. Tobacco taxation could have substantial health and economic benefits to RI communities, but perhaps is not culturally-appropriate. In order to better support RI communities, governments and other organizations need to examine this policy instrument in the context of RI populations.

  8. Teen Pregnancy Prevention Program Recommendations from Urban and Reservation Northern Plains American Indian Community Members

    OpenAIRE

    McMahon, Tracey R.; Hanson, Jessica D.; Griese, Emily R.; Kenyon, DenYelle Baete

    2015-01-01

    Despite declines over the past few decades, the United States has one of the highest rates of teen pregnancy compared to other industrialized nations. American Indian youth have experienced higher rates of teen pregnancy compared to the overall population for decades. Although it's known that community and cultural adaptation enhance program effectiveness, few teen pregnancy prevention programs have published on recommendations for adapting these programs to address the specific needs of Nort...

  9. The miRNAome dynamics during developmental and metabolic reprogramming of tomato root infected with potato cyst nematode.

    Science.gov (United States)

    Koter, Marek D; Święcicka, Magdalena; Matuszkiewicz, Mateusz; Pacak, Andrzej; Derebecka, Natalia; Filipecki, Marcin

    2018-03-01

    results indicate a large regulatory potential for miRNAs in tuning the development and defense responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Investigating intra-tumor heterogeneity and expression gradients of miR-21, miR-92a and miR-200c and their potential of predicting lymph node metastases in early colorectal cancer

    DEFF Research Database (Denmark)

    Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg

    2016-01-01

    Introduction miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels...... in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC. Material and methods Two parallel studies on archived formalin-fixed paraffin......-embedded (FFPE) CRC tissue. Intra-tumor and inter-patient variances were analyzed in 9 early metastatic CRCs by measuring expression levels by qRT-PCR on isolated tissue samples from luminal, central and invasive border zones. Associations between miRNA expression levels and early metastasizing tumors...

  11. The miRNA Pull Out Assay as a Method to Validate the miR-28-5p Targets Identified in Other Tumor Contexts in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Milena Rizzo

    2017-01-01

    Full Text Available miR-28-5p is an intragenic miRNA which is underexpressed in several tumor types showing a tumor suppressor (TS activity. Routinely, the known miR-28-5p targets are validated in specific tumor contexts but it is unclear whether these targets are also being regulated in other tumor types. To this end, we adopted the miRNA pull out assay to capture the miR-28-5p targets in DU-145 prostate cancer (PCa cells. Firstly, we demonstrated that miR-28-5p acts as a TS-miRNA in PCa, affecting cell proliferation, survival, and apoptosis. Secondly, we evaluated the enrichment of the 10 validated miR-28-5p targets in the pull out sample. We showed that E2F6, TEX-261, MAPK1, MPL, N4BP1, and RAP1B but not BAG1, OTUB1, MAD2L1, and p21 were significantly enriched, suggesting that not all the miR-28-5p targets are regulated by this miRNA in PCa. We then verified whether the miR-28-5p-interacting targets were regulated by this miRNA. We selected E2F6, the most enriched target in the pull out sample, and demonstrated that miR-28-5p downregulated E2F6 at the protein level suggesting that our approach was effective. In general terms, these findings support the miRNA pull out assay as a useful method to identify context-specific miRNA targets.

  12. An electrochemical ELISA-like immunosensor for miRNAs detection based on screen-printed gold electrodes modified with reduced graphene oxide and carbon nanotubes.

    Science.gov (United States)

    Tran, H V; Piro, B; Reisberg, S; Huy Nguyen, L; Dung Nguyen, T; Duc, H T; Pham, M C

    2014-12-15

    We design an electrochemical immunosensor for miRNA detection, based on screen-printed gold electrodes modified with reduced graphene oxide and carbon nanotubes. An original immunological approach is followed, using antibodies directed to DNA.RNA hybrids. An electrochemical ELISA-like amplification strategy was set up using a secondary antibody conjugated to horseradish peroxidase (HRP). Hydroquinone is oxidized into benzoquinone by the HRP/H2O2 catalytic system. In turn, benzoquinone is electroreduced into hydroquinone at the electrode. The catalytic reduction current is related to HRP amount immobilized on the surface, which itself is related to miRNA.DNA surface density on the electrode. This architecture, compared to classical optical detection, lowers the detection limit down to 10 fM. Two miRNAs were studied: miR-141 (a prostate biomarker) and miR-29b-1 (a lung cancer biomarker). Copyright © 2014 Elsevier B.V. All rights reserved.

  13. A synthesis of ethnohistorical materials concerning the administration of Federal Indian policy among the Yakima, Umatilla, and Nez Perce Indian people: Working draft

    International Nuclear Information System (INIS)

    Liebow, E.B.; Younger, C.A.; Broyles, J.A.

    1987-11-01

    For the purposes of the Nuclear Waste Policy Act, the Confederated Tribes and Bands of the Yakima Indian Nation, the Confederated Tribes of the Umatilla Indian Reservation, and the Nez Perce Tribe have been accorded the status of ''Affected Indian Tribe'' and have become party to the proceedings to determine a suitable location for the nation's first commercial waste repository. Each of the Tribes has expressed concerns about the suitability of the Hanford Site in eastern Washington. These concerns, in general, address the proposed repository's effects on traditional spiritual beliefs and cultural practices, on tribal sovereignty and the Tribes' right to self-government, on the natural resources under tribal management jurisdiction, and on the health and socioeconomic characteristics of the Tribes' reservation communities. The Yakima, Umatilla, and Nez Perce have distinctive cultural traditions that may be adversely affected by activities related to the Basalt Waste Isolation Project (BWIP). Further, the Tribes enjoy a unique relationship with the federal government. Because of their distinctive cultures and governmental status, particular attention will be paid to expressed interests of the Tribes, and to ways in which these interests may be affected by the repository program. Monitoring is needed to describe current conditions among the Affected Tribes' populations, to describe BWIP site characterization activities affecting the Tribes, and to measure any changes in these conditions that may occur as a direct result of site characterization. This paper reports our first efforts at gathering historical information. It summarizes materials contained in two sources: the reports of field agents to the Commissioner of Indian Affairs (1854-1936), and the dockets of the Indian Claims Commission. 24 refs., 3 figs

  14. Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

    Directory of Open Access Journals (Sweden)

    Ahmed Hussein Zedan

    Full Text Available In the last decade microRNAs (miRNAs have been widely investigated in prostate cancer (PCa and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome.Prostatectomy specimens and matched, preoperative needle biopsies from a retrospective cohort of 49 patients, who underwent curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145 using tissue micro-array (TMA and in situ hybridization (ISH. Inter- and intra-patient variation was assessed using intra-class correlation (ICC.Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH, and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0.72. The ICC varied from 0.451 to 0.764, with miRNA-34a showing an intra-tumoral heterogeneity accounting for less than 50% of the total variation. Regarding clinicopathological outcomes, only miRNA-143 showed potential as a prognostic marker with a higher expression correlating with longer relapse-free survival (p = 0.016.The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra-tumoral heterogeneity in the expression of various miRNAs calling for caution when using these tumor tissue biomarkers in prognostic and predictive settings.

  15. Molecular characterization and expression analysis of a GTP-binding protein (MiRab5) in Mangifera indica.

    Science.gov (United States)

    Liu, Zhao-liang; Luo, Cong; Dong, Long; Van Toan, Can; Wei, Peng-xiao; He, Xin-hua

    2014-04-25

    The Rab family, the largest branch of Ras small GTPases, plays a crucial role in the vesicular transport in plants. The members of Rab family act as molecular switches that regulate the fusion of vesicles with target membranes through conformational changes. However, little is known about the Rab5 gene involved in fruit ripening and stress response. In this study, the MiRab5 gene was isolated from stress-induced Mangifera indica. The full-length cDNA sequence was 984bp and contained an open reading frame of 600bp, which encoded a 200 amino acid protein with a molecular weight of 21.83kDa and a theoretical isoelectric point of 6.99. The deduced amino acid sequence exhibited high homology with tomato (91% similarity) and contains all five characteristic Rab motifs. Real-time quantitative RT-PCR analysis demonstrated that MiRab5 was ubiquitously expressed in various mango tree tissues at different levels. The expression of MiRab5 was up-regulated during later stages of fruit ripening. Moreover, MiRab5 was generally up-regulated in response to various abiotic stresses (cold, salinity, and PEG treatments). Recombinant MiRab5 protein was successfully expressed and purified. SDS-PAGE and western blot analysis indicated that the expressed protein was recognized by the anti-6-His antibody. These results provide insights into the role of the MiRab5 gene family in fruit ripening and stress responses in the mango plant. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    Directory of Open Access Journals (Sweden)

    Yunpeng Zhang

    2015-01-01

    Full Text Available Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM, to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

  17. Taking a multiple intelligences (MI) perspective.

    Science.gov (United States)

    Gardner, Howard

    2017-01-01

    The theory of multiple intelligences (MI) seeks to describe and encompass the range of human cognitive capacities. In challenging the concept of general intelligence, we can apply an MI perspective that may provide a more useful approach to cognitive differences within and across species.

  18. miRNA genes of an invasive vector mosquito, Aedes albopictus.

    Directory of Open Access Journals (Sweden)

    Jinbao Gu

    Full Text Available Aedes albopictus, a vector of Dengue and Chikungunya viruses, is a robust invasive species in both tropical and temperate environments. MicroRNAs (miRNAs regulate gene expression and biological processes including embryonic development, innate immunity and infection. While a number of miRNAs have been discovered in some mosquitoes, no comprehensive effort has been made to characterize them from different developmental stages from a single species. Systematic analysis of miRNAs in Ae. albopictus will improve our understanding of its basic biology and inform novel strategies to prevent virus transmission. Between 10-14 million Illumina sequencing reads per sample were obtained from embryos, larvae, pupae, adult males, sugar-fed and blood-fed adult females. A total of 119 miRNA genes represented by 215 miRNA or miRNA star (miRNA* sequences were identified, 15 of which are novel. Eleven, two, and two of the newly-discovered miRNA genes appear specific to Aedes, Culicinae, and Culicidae, respectively. A number of miRNAs accumulate predominantly in one or two developmental stages and the large number that showed differences in abundance following a blood meal likely are important in blood-induced mosquito biology. Gene Ontology (GO analysis of the targets of all Ae. albopictus miRNAs provides a useful starting point for the study of their functions in mosquitoes. This study is the first systematic analysis of miRNAs based on deep-sequencing of small RNA samples of all developmental stages of a mosquito species. A number of miRNAs are related to specific physiological states, most notably, pre- and post-blood feeding. The distribution of lineage-specific miRNAs is consistent with mosquito phylogeny and the presence of a number of Aedes-specific miRNAs likely reflects the divergence between the Aedes and Culex genera.

  19. Targeted delivery of miR-200c/DOC to inhibit cancer stem cells and cancer cells by the gelatinases-stimuli nanoparticles.

    Science.gov (United States)

    Liu, Qin; Li, Ru-Tian; Qian, Han-Qing; Wei, Jia; Xie, Li; Shen, Jie; Yang, Mi; Qian, Xiao-Ping; Yu, Li-Xia; Jiang, Xi-Qun; Liu, Bao-Rui

    2013-09-01

    Cancer stem cells (CSCs) are recently discovered as vital obstacles for the successful cancer therapy. Emerging evidences suggest that miR-200c functions as an effective CSCs inhibitor and can restore sensitivity to microtubule-targeting drugs. In the present work, the intelligent gelatinases-stimuli nanoparticles (NPs) was set up to co-deliver miR-200c and docetaxel (DOC) to verify their synergetic effects on inhibition of CSCs and non-CSC cancer cells. After tumor cells were treated with miR-200c NPs, miR-200c and its targeted gene class III beta-tubulin (TUBB3)TUBB3 expression were evaluated. The effects of miR-200c/DOC NPs on tumor cell viability, migration and invasion as well as the expression of E-cadherin and CD44 were studied. The antitumor effects of miR-200c/DOC NPs were compared with DOC NPs in xenograft gastric cancer mice. Moreover, the residual tumors after treatment were subcutaneously seeded into nude mice to further investigate the effective maintenance of NPs. We found that the gelatinases-stimuli NPs facilitated miR-200c into cells, achieving sustained miR-200c expression in tumor cells during 9 days. The miR-200c/DOC NPs significantly enhanced cytotoxicity of DOC, possibly by decreasing TUBB3 level, and reversing EMT. The miR-200c NPs achieved high levels of in vivo accumulation and long retention in gastric cancer xenografts after intravenous administration. The miR-200c/DOC NPs prominently suppressed in vivo tumor growth with elevated miR-200c and E-cadherin levels and down-regulated TUBB3 and CD44 expressions. When the residual tumors after miR-200c/DOC NPs treatment were re-transplanted into nude mice, the tumors demonstrated the slowest growth speed. The miR-200c/DOC NPs may provide a promising modality for co-delivery of nucleic acid and drugs to simultaneously inhibit CSCs and non-CSC cancer cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. MiR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?

    International Nuclear Information System (INIS)

    Cizeron-Clairac, Geraldine; Lallemand, François; Vacher, Sophie; Lidereau, Rosette; Bieche, Ivan; Callens, Celine

    2015-01-01

    MicroRNAs (miRNAs) show differential expression across breast cancer subtypes and have both oncogenic and tumor-suppressive roles. Numerous microarray studies reported different expression patterns of miRNAs in breast cancers and found clinical interest for several miRNAs but often with contradictory results. Aim of this study is to identify miRNAs that are differentially expressed in estrogen receptor positive (ER + ) and negative (ER − ) breast primary tumors to better understand the molecular basis for the phenotypic differences between these two sub-types of carcinomas and to find potential clinically relevant miRNAs. We used the robust and reproductive tool of quantitative RT-PCR in a large cohort of well-annotated 153 breast cancers with long-term follow-up to identify miRNAs specifically differentially expressed between ER + and ER − breast cancers. Cytotoxicity tests and transfection experiments were then used to examine the role and the regulation mechanisms of selected miRNAs. We identified a robust collection of 20 miRNAs significantly deregulated in ER + compared to ER − breast cancers : 12 up-regulated and eight down-regulated miRNAs. MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER + compared to ER − with a fold change upper to 23. It was also significantly up-regulated in ER + /Normal breast tissue and down-regulated in ER − /Normal breast tissue. Functional experiments showed that miR-190b expression is not directly regulated by estradiol and that miR-190b does not affect breast cancer cell lines proliferation. Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status. This study reveals miR-190b as the highest up-regulated miRNA in hormone-dependent breast cancers. Due to its specificity and high expression level, miR-190b could therefore represent a new biomarker in hormone-dependent breast cancers but its exact role carcinogenesis remains to