2,474 research outputs found

    Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

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    Abstract Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.http://deepblue.lib.umich.edu/bitstream/2027.42/78313/1/1471-2407-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78313/2/1471-2407-10-614.pdfPeer Reviewe

    3D Face Reconstruction from Single 2D Image Using Distinctive Features

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    3D face reconstruction is considered to be a useful computer vision tool, though it is difficult to build. This paper proposes a 3D face reconstruction method, which is easy to implement and computationally efficient. It takes a single 2D image as input, and gives 3D reconstructed images as output. Our method primarily consists of three main steps: feature extraction, depth calculation, and creation of a 3D image from the processed image using a Basel face model (BFM). First, the features of a single 2D image are extracted using a two-step process. Before distinctive-features extraction, a face must be detected to confirm whether one is present in the input image or not. For this purpose, facial features like eyes, nose, and mouth are extracted. Then, distinctive features are mined by using scale-invariant feature transform (SIFT), which will be used for 3D face reconstruction at a later stage. Second step comprises of depth calculation, to assign the image a third dimension. Multivariate Gaussian distribution helps to find the third dimension, which is further tuned using shading cues that are obtained by the shape from shading (SFS) technique. Thirdly, the data obtained from the above two steps will be used to create a 3D image using BFM. The proposed method does not rely on multiple images, lightening the computation burden. Experiments were carried out on different 2D images to validate the proposed method and compared its performance to those of the latest approaches. Experiment results demonstrate that the proposed method is time efficient and robust in nature, and it outperformed all of the tested methods in terms of detail recovery and accuracy

    Indigenous uses of medicinal plants in Tarikhet block of Kumaun Himalaya, India

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    Over 80% of the world population relies on vegetation for health care; more than 30% of the entire plant species are used for medicinal purposes. India displays large topography and various climatic conditions which accommodates more than 45,000 species. Uttarakhand state known as the ‘natural reservoir of India’ is in north-western Himalaya; it has 8000 vascular plants species, over 1748 of these are known for their therapeutic properties. In hilly areas of Uttarakhand, local communities still use the ethno-medicinal plants to cure various diseases and ailments. Although several researchers have conducted surveys across different areas of the Himalayan region, and to our knowledge, ethno-medicinal plants’ studies have not been conducted in Tarikhet block of Almora district, Uttarakhand. In this study, a total of 155 individuals of different age groups (20–93 years) with different socio-economic status (farmer, service man, ex-service man, businessman, housewives, students) participated. A total of 72 medicinal plant species were reported from which 31 were herbs, 20 trees, 15 shrubs and 6 were climbers belonging to 44 families used in the treatment of various ailments. Furthermore, we recorded that local people used various plant parts that is, leaves (35), fruit (15), root (10), whole plant (5), seed (6), bark (6) stem (4), rhizome (3) and others (4), to treat a wide range of health conditions. Thus, documenting the ethno-medicinal plants and for conservation is of the upmost important not only for cultural traditions and for biodiversity conservation. The study shows that locals have extensive ethnobotanical knowledge and are highly dependent on the forest for their livelihood. The valuable knowledge is anchored in cultural practices and orally transmitted from one generation to another; however, the loss is imminent as the new generation lacks the interest and the traditional ethnobotanical knowledge is unprotected.info:eu-repo/semantics/publishedVersio

    Atherosclerosis and plaque rupture: An update

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    Intravascular ultrasound aids in the performance of endovascular repair of abdominal aortic aneurysm

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    AbstractPurpose: The purpose of this retrospective review was to assess the accuracy of aortic measurements with intravascular ultrasound scan (IVUS) compared with computed tomographic (CT) scan and to assess the role of IVUS in the performance of endovascular repair of abdominal aortic aneurysms (AAAs). Methods: Seventy-eight patients undergoing repair of AAA with the AneuRx stent graft (Medtronic AVE, Inc, Santa Rosa, Calif) underwent measurement with CT scan and IVUS. The initial selection of stent graft size was made on the basis of the CT scan measurements, but the final decision for size was made on the basis of the IVUS measurements. Standard measurements of a phantom tube obtained with IVUS, CT scan, and digital caliper were also compared. Results: IVUS measurements of the phantom standard agreed closely with CT scan measurements. However, stent graft size initially selected with CT measurement was altered in 28% of cases on the basis of intraoperative IVUS measurements. No type I endoleaks were encountered in our series, and no aortic cuffs were necessary for endoleak repair. Conclusion: IVUS accurately measures the aorta for selection of stent grafts for endovascular repair of AAA and may prevent type I endoleaks and remedial procedures for their repair. (J Vasc Surg 2003;37:615-8

    EFFECT OF NON-ENZYMATIC ANTIOXIDANTS IN EXTENDER ON POST-THAW QUALITY OF BUFFALO (BUBALUS BUBALIS) BULL SPERMATOZOA

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    The objective of the present study was to determine the effect of non-enzymatic antioxidants (vitamin C or E) in tris-citric acid buffer (TCA) on post-thaw quality of buffalo (Bubalus bubalis) bull spermatozoa. Split pooled buffalo bull ejaculates were diluted in TCA egg yolk glycerol extender containing either vitamin C (TCAC), vitamin E (TCAE) or without antioxidant (TCAN) at 37°C. Extended semen was cooled to 4C in 2 h and equilibrated for 4 h at 4C. Cooled semen was then filled in 0.5 ml straws at 4C and frozen in programmable cell freezer. Thawing of semen was performed at 37°C for 30 seconds. Sperm motility, plasma membrane integrity and sperm morphology (acrosome integrity, head, mid-piece and tail abnormalities) of each semen sample were evaluated. Percentage of post-thaw spermatozoal motility assessed visually at 0 and 6 h and the post-thaw percentage of spermatozoa with intact plasma membranes at 0 h were higher (P<0.05) with TCAC and TCAE compared to control. However, the differences in both these parameters between the former two groups was non significant. The post-thaw percentage of spermatozoa with normal acrosomes was higher (P<0.05) in TCAE extender than control. Mean sperm abnormalities in samples cryopreserved with extender having TCAC, TCAE or TCAN were similar (P>0.05). In conclusion, non-enzymatic antioxidants, particularly vitamin E, in the tris citric acid extender may improve the quality of frozen-thawed buffalo bull spermatozoa

    Extending in Silico Protein Target Prediction Models to Include Functional Effects.

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    In silico protein target deconvolution is frequently used for mechanism-of-action investigations; however existing protocols usually do not predict compound functional effects, such as activation or inhibition, upon binding to their protein counterparts. This study is hence concerned with including functional effects in target prediction. To this end, we assimilated a bioactivity training set for 332 targets, comprising 817,239 active data points with unknown functional effect (binding data) and 20,761,260 inactive compounds, along with 226,045 activating and 1,032,439 inhibiting data points from functional screens. Chemical space analysis of the data first showed some separation between compound sets (binding and inhibiting compounds were more similar to each other than both binding and activating or activating and inhibiting compounds), providing a rationale for implementing functional prediction models. We employed three different architectures to predict functional response, ranging from simplistic random forest models ('Arch1') to cascaded models which use separate binding and functional effect classification steps ('Arch2' and 'Arch3'), differing in the way training sets were generated. Fivefold stratified cross-validation outlined cascading predictions provides superior precision and recall based on an internal test set. We next prospectively validated the architectures using a temporal set of 153,467 of in-house data points (after a 4-month interim from initial data extraction). Results outlined Arch3 performed with the highest target class averaged precision and recall scores of 71% and 53%, which we attribute to the use of inactive background sets. Distance-based applicability domain (AD) analysis outlined that Arch3 provides superior extrapolation into novel areas of chemical space, and thus based on the results presented here, propose as the most suitable architecture for the functional effect prediction of small molecules. We finally conclude including functional effects could provide vital insight in future studies, to annotate cases of unanticipated functional changeover, as outlined by our CHRM1 case study.LM thanks the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/K011804/1); and AstraZeneca, grant number RG75821

    Izvala maternice i rodnice u križanih krava: prevalencija, klinička slika i liječenje preinačenim Bühnerovim postupkom upotrebom infuzijske cjevčice kao šivaćeg materijala.

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    Eighty-six cows presented for treatment of genital prolapse (uterine - 44 and vaginal - 42) were included in this study. Vaginal prolapse mostly occurred during advanced pregnancy and uterine prolapse following parturition. At the time of examination, most of the animals with uterine prolapse were recumbent, while those with vaginal prolapse were standing. The highest prevalence of genital prolapse was recorded in crossbred Jersey cows around the 2nd parturition during the autumn season. The number of cases with grade 1 vaginal prolapse was highest (52.38%) followed by grade 3 (33.33%) and grade 2 (14.29%) respectively. Grade 1 vaginal prolapse could be managed successfully by exogenous progesterone therapy (500 mg hydroxyprogesterone i.m. two times at weekly interval) along with hind quarter elevation in 45.45% cases (10/22); however, in the remaining 54.55% cases the prolapse was converted to grade 2. A few (27%) animals with uterine prolapse were simultaneously suffering from milk fever, dystocia and retained fetal membranes. In all the cows with grade 2 and 3 vaginal prolapse, and also those with uterine prolapse, the mass was repositioned following the standard technique under caudal epidural analgesia. A modified Bühner’s technique, using sterile infusion set tubing as suture material, was effective in retention of the mass in all the cows. Complications and disfigurement of the vulvar area were not noticed, even in cases where the suture was kept in-situ for a prolonged period.U istraživanje je bilo uključeno 86 krava: 44 s izvalom maternice, a 42 s izvalom rodnice. Izvala rodnice pretežno se javljala u visokom stupnju bređosti, a maternice nakon telenja. Za vrijeme pretrage većina krava s izvalom maternice je ležala, dok su one s izvalom rodnice stajale. Izvala spolnih organa najčešće je ustanovljena u križanih Jersey krava prilikom drugoga telenja i to u jesen. Broj slučajeva prvog stupnja izvale rodnice bio je najveći (52,38%). Slijedi broj izvala trećeg stupnja (33,33%) te drugog stupnja (14,29%). Prvi stupanj izvale rodnice bio je uspješno izliječen u 45,45% slučajeva (10/22) davanjem 500 mg hidroksiprogesterona intramuskularno dvaput tjedno uz podizanje stražnjeg dijela tijela. U ostalih 54,55% slučajeva izvala je prešla u drugi stupanj. U manjeg broja (27%) životinja s izvalom maternice bila je ustanovljena mliječna vrućica, težak porođaj i zaostajanje posteljice. U svih krava s drugim i trećim stupnjem izvale rodnice i onih s izvalom maternice, organi su bili vraćeni u normalan položaj standardnim postupkom uz kaudalnu epiduralnu anesteziju. Preinačen Bühnerov postupak upotrebom sterilne infuzijske cjevčice kao šivaćeg materijala pokazao se učinkovitim u liječenju svih krava. Komplikacije i promjene oblika stidnice nisu primijećene čak ni u slučajevima kad je šav duže vrijeme ostao in situ
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