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1
Lang, K. M., and R. A. Spritz. "In vitro splicing pathways of pre-mRNAs containing multiple intervening sequences?" Molecular and Cellular Biology 7, no. 10 (October 1987): 3428–37. http://dx.doi.org/10.1128/mcb.7.10.3428.
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We analyzed the in vitro splicing pathways of three multi-intervening-sequence (IVS) pre-mRNAs: human beta-globin, which contains two IVSs (K. M. Lang, V. L. van Santen, and R. A. Spritz, EMBO J. 4:1991-1996, 1985); rat alpha-lactalbumin, which contains three IVSs; and murine interleukin-3, which contains four IVSs. We found that there are highly preferred pathways of IVS removal from these multi-IVS pre-mRNAs in vitro. The three IVSs of rat alpha-lactalbumin pre-mRNA were excised sequentially from 5' to 3'; in most molecules, IVS1 was removed first, followed by IVS2 and finally by IVS3. The splicing pathway of interleukin-3 pre-mRNA in vitro was more complex. The four IVSs were excised in a highly preferred temporal order, but the order was not strictly sequential or directional. In most molecules, IVS1 and IVS4 were removed first, either simultaneously or in rapid succession. Subsequently, IVS2 was excised, followed by IVS3. The observed splicing pathways apparently resulted from differences in lag times and maximum excision rates of the different IVSs. We detected no exon skipping during splicing of these transcripts in vitro. These observations have implication for proposed models of splice site selection.
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Lang, K. M., and R. A. Spritz. "In vitro splicing pathways of pre-mRNAs containing multiple intervening sequences?" Molecular and Cellular Biology 7, no. 10 (October 1987): 3428–37. http://dx.doi.org/10.1128/mcb.7.10.3428-3437.1987.
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We analyzed the in vitro splicing pathways of three multi-intervening-sequence (IVS) pre-mRNAs: human beta-globin, which contains two IVSs (K. M. Lang, V. L. van Santen, and R. A. Spritz, EMBO J. 4:1991-1996, 1985); rat alpha-lactalbumin, which contains three IVSs; and murine interleukin-3, which contains four IVSs. We found that there are highly preferred pathways of IVS removal from these multi-IVS pre-mRNAs in vitro. The three IVSs of rat alpha-lactalbumin pre-mRNA were excised sequentially from 5' to 3'; in most molecules, IVS1 was removed first, followed by IVS2 and finally by IVS3. The splicing pathway of interleukin-3 pre-mRNA in vitro was more complex. The four IVSs were excised in a highly preferred temporal order, but the order was not strictly sequential or directional. In most molecules, IVS1 and IVS4 were removed first, either simultaneously or in rapid succession. Subsequently, IVS2 was excised, followed by IVS3. The observed splicing pathways apparently resulted from differences in lag times and maximum excision rates of the different IVSs. We detected no exon skipping during splicing of these transcripts in vitro. These observations have implication for proposed models of splice site selection.
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Shapoval, T. V. "Legal nature of the ivsc international standards." Uzhhorod National University Herald. Series: Law, no. 63 (August 9, 2021): 171–77. http://dx.doi.org/10.24144/2307-3322.2021.63.30.
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The article is focused on legal nature of International Valuation Standards Committee (renamed to International Valuation Standards Council in 2008) and implementation of its valuation standards by states and international organizations. The paper concentrates on legal gaps regarding the application aspects of property value calculations in international law. Treaties do not provide substantial determinacy, include no instruction or the appropriate methodology on numerous calculation issues and typically set forth only basic standard of valuation such as standard of fair market value of property for the calculation of compensation. It shows that lack of standards for determining awards of compensation creates a source of uncertainty for protection in international public law. The issue discusses a framework where international valuation standards of international non-governmental organizations are given legal weight and serve as guidelines for the calculation of awards. After establishing the legal basis for an award, tribunals use their impression of valuation best practices as well as discretion to conduct the analysis. The result depends on the assumptions and philosophy of the adjudicating tribunal. It is emphasized that international arbitration practice in measures of compensation should be based on principles of fairness and reasonableness.
Part of the issue is based on Directive of European Union with provisions that valuation standards of states should take into account internationally recognised valuation standards, in particular those developed by the International Valuation Standards Committee, the European Group of Valuers’ Associations or the Royal Institution of Chartered Surveyors. Member states of European Union admitted valuation standards of international non-governmental organizations as reliable standards for the credit purposes after the financial crisis, which has shown that irresponsible behaviour by market participants can undermine the foundations of the financial system leading to potentially severe social and economic consequences.
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Bearman, David. "Unveiling the products of cooperation: IVSC and MEC." Archives and Museum Informatics 4, no. 2 (June 1990): 7–8. http://dx.doi.org/10.1007/bf02806249.
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Chew, Sin Chi, Onkar Singh, Xiangai Chen, Wan-Teck Lim, Eng-Huat Tan, Edmund Jon Deoon Lee, and Balram Chowbay. "Docetaxel pharmacogenetics: The influence of RXRα and HNF4α genetic variations on docetaxel disposition in Asian nasopharyngeal carcinoma patients." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 2598. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.2598.
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2598 Background: The transactivations of the metabolism enzymes (CYP3A4/5) and efflux transporters (ABCB1/ABCC2) involved in docetaxel disposition are regulated by the orphan nuclear receptors such as PXR, CAR, RXRα and HNF4α. This study aimed to explore the associations between the genetic variations present in the genes encoding the orphan nuclear receptors, RXRα and HNF4α, on docetaxel disposition. Methods: The DNAs from healthy Chinese, Malay and Indian subjects (n=56 each) were screened for RXRα and HNF4α SNPs in exons and intronic/exonic boundaries by direct sequencing. The high frequency SNPs (>1%) were profiled in a cohort of local nasopharyngeal cancer patients (n=54). Genotypic-phenotypic correlations were conducted using Mann-Whitney U-test and Kruskal-Wallis test. Results: Eighty-eight and sixty-nine SNPs were identified from the healthy screening of RXRα and HNF4α, respectively, across 3 populations. A total of 30 and 35 high frequency SNPs in RXRα and HNF4α, respectively, were profiled in the patients. Six RXRα SNPs [IVS2+33G>A (rs2234753), IVS7+70A>G (rs1536475),*846G>A (rs4240711), *+4458G>A (rs3132291), *+4768C>A (rs4842196) and *+4988A>G (rs4842198)] and 6 HNF4α SNPs [-728A>C (rs1800963), IVS2-278A>G (rs55934816), IVS6+141A>G (rs6103731), IVS7-88T>C (rs2273618), IVS9–145T>C (rs3746574) and IVS9-67C>G (rs3746575)] were significantly associated with higher clearance and lower AUC0-∞ and/or Cmax of docetaxel (P<0.05). Conversely, HNF4α SNP [IVS9+354G>T (rs3818247)] was associated with lower clearance and higher AUC0-∞ and Cmax of docetaxel (p<0.05). A high linkage pattern was observed among the abovementioned RXRα SNPs except for IVS2+33G>A (rs2234753) (D'≥0.74). Similarly, HNF4α SNPs were found to be highly linked, except for -728A>C (rs1800963) (D'≥0.62). Conclusions: The results highlight the contributions of RXRα and HNF4α pharmacogenetics in influencing the inter-individual variability in docetaxel disposition in Asian nasopharyngeal patients.
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Ma, Suk Ling, Nelson Leung Sang Tang, Linda Chiu Wa Lam, and Helen Fung Kum Chiu. "Polymorphisms of the cholesterol 24-hydroxylase (CYP46A1) gene and the risk of Alzheimer's disease in a Chinese population." International Psychogeriatrics 18, no. 1 (February 15, 2006): 37–45. http://dx.doi.org/10.1017/s1041610205003108.
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Background: An increasing number of studies have suggested a link between cholesterol metabolism and Alzheimer's disease (AD), which may be mediated by its effect on amyloid processing. Intracranial cholesterol is primarily eliminated into the bloodstream through conversion into 24-hydroxycholesterol by the enzyme cholesterol 24-hydroxylase (encoded by the CYP46A1 gene). CYP46A1 is an essential gene modulating cholesterol metabolism in the brain.Method: To investigate whether polymorphisms in the CYP46A1 gene modulate the risk of AD, we studied four common polymorphisms (IVS1-192, IVS2-150, IVS3-128 and IVS4-122) in 182 Chinese AD patients and 179 age-matched healthy Chinese subjects.Results and conclusion: We found that the IVS3-128 polymorphism was associated with the risk of AD (p < 0.05). Subjects homozygous for the C alleles were protected from AD with an adjusted odds ratio (OR) of 1.53 [95% confidence interval (95% CI) 0.98–2.37, p = 0.047]. However, another minor allele, IVS1-192 C, was more prevalent in the AD group and was associated with an increased risk. Haplotype analysis revealed that two of the eight common haplotypes formed by the four polymorphisms were rarely found in the AD group, suggesting a protective effect of these two haplotypes (GTCA and CCTA). The results supported the involvement of the CYP46A1 gene and cholesterol metabolism in the pathogenesis of AD.
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French, Nick, and Laura Gabrielli. "Pricing to market." Journal of Property Investment & Finance 36, no. 4 (July 2, 2018): 391–96. http://dx.doi.org/10.1108/jpif-05-2018-0033.
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Purpose Since the global financial economic crisis hit the world markets in 2007/2008, the role of property valuation has been under greater and greater scrutiny. The process of valuation and its quality assurance has been addressed by the higher prominence of the International Valuation Standards Council (IVSC). This is a significant initiative worldwide. However, there has been little written on the appropriate use of valuation approaches and methods in market valuations. There is now a hierarchy of valuation definitions. In order, there are valuation approaches, valuation methods and, as a subset of the methods, techniques or models. The purpose of this paper is to look at the importance of identifying the appropriate approach to be adopted in market valuations and the methods, techniques and models that should be applied to determine market value. Design/methodology/approach This practice briefing is an overview of the valuation approaches, methods and models available to the valuer and comments on the appropriateness of valuation each in assessing market value. Findings This paper reviews the IVSC-recognised approaches and prompts the valuer to be careful with the semantics involved so that they are better placed to provide an unambiguous service to their clients. Practical implications The role of the valuer in practice is to identify the appropriate approach for the valuation of the subject property, choose the right method and then apply the correct mathematical model for the valuation task in hand. Originality/value This provides guidance on how valuations can be presented to the client in accordance with the International Valuation Standards.
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Kafle, Pankaj, MA Ansari, and U. Khanal. "Fetal Cardiac Interventricular Septal Thickness at 28–37 Weeks of Gestation in Nepalese Population." Nepalese Journal of Radiology 2, no. 2 (March 3, 2013): 36–42. http://dx.doi.org/10.3126/njr.v2i2.7683.
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Objective: The purpose of this study is to establish a new reference range for fetal interventricular septal thickness in uncomplicated pregnancy at 28-37 weeks of gestation. Materials and Methodology: This was a prospective cross sectional study involving 300 singleton pregnancies between 28-37 weeks of gestation without any known risk factors of adverse pregnancy outcome who were referred for routine obstetric examination. The protocol included the prenatal 2-dimensional M-mode echocardiographic measurements of fetal IVST and data were used to construct the normograms and percentile fitted curves for different gestational age. The relationship between the IVSD and IVSS and gestational age were determined. Results: A total of 300 measurements were obtained. The normal values of the IVSD and IVSS according to gestational age were presented as 5th, 50th and 95th percentile ranks. The correlation coefficients (r) between the IVSD and IVSS and gestational age were 0.19 and 0.14, respectively. The weak correlation may be probably due to small sample size. The IVSD and IVSS were not statistically different with advancing gestation. The 95th percentile of the IVSD was 4.57 millimeters (mm) (range =4.12 to 4.62 mm) and IVSS was 6.67 mm (range = 5.81 to 6.77 mm). Conclusion: The normal values of fetal IVSD and IVSS in a Nepalese population from 28 to 37 weeks’ gestation were established. This could be used as a baseline data in detecting the asymmetrical septal hypertrophy during fetal life. Nepalese Journal of Radiology; Vol. 2; Issue 2; July-Dec. 2012; 36-42 DOI: http://dx.doi.org/10.3126/njr.v2i2.7683
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Bø, Nils Kristian, and Finn Espen Sellæg. "«Virkelig verdi»-målinger – Utviklingen innen standardisering av verdsettelser med hovedvekt på høringsutkast fra IASB og IVSC." Praktisk økonomi & finans 27, no. 02 (August 17, 2011): 69–83. http://dx.doi.org/10.18261/issn1504-2871-2011-02-07.
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Ali, Akhtar, Subodh Kumar Singh, and Rajiva Raman. "Coding Region of IRF6 Gene May Not Be Causal for Van Der Woude Syndrome in Cases from India." Cleft Palate-Craniofacial Journal 46, no. 5 (September 2009): 541–44. http://dx.doi.org/10.1597/08-202.1.
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Objective: Evaluation of the IRF6 gene in Van der Woude syndrome cases from an Indian population. Subjects: Nine affected and four unaffected individuals from seven families with Van der Woude syndrome as well as five normal controls (with no history of Van der Woude or any other congenital malformation and belonging to the same geographical area as the families with Van der Woude syndrome). Method: Direct sequencing of all coding regions and exon-intron boundaries of the IRF6 gene. Results: Five novel variants: IVS1+3900 A>G, 191 T>C, IVS4+775 C>T, IVS8+218 C>T, 1511 T>A (Ser 416 Arg) and two known variants: IVS6+27 C>G, 1083 G>A (V274I) were detected. Except for one, all were in noncoding regions either in 3′UTR or in introns. There was only one mutation in the coding region, detected in a normal control. Conclusion: The present report indicates that point mutations in the coding region of the IRF6 gene may not be a major cause of Van der Woude syndrome in Indian populations.
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Михайлова, С. В., and S. V. Mikhailova. "Estimation of a potential functional significance for the IVS2(+4) t/c, IVS4(-44) t/c и IVS5(-47) a/g polymorphisms of the HFE human hereditary hemochromatosis gene." Mathematical Biology and Bioinformatics 3, no. 2 (December 1, 2008): 60–68. http://dx.doi.org/10.17537/2008.3.60.
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Pandey, Manish K., Rakesh Kumar, Arun K. Pandey, Pooja Soni, Sunil S. Gangurde, Hari K. Sudini, Jake C. Fountain, et al. "Mitigating Aflatoxin Contamination in Groundnut through A Combination of Genetic Resistance and Post-Harvest Management Practices." Toxins 11, no. 6 (June 3, 2019): 315. http://dx.doi.org/10.3390/toxins11060315.
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Aflatoxin is considered a “hidden poison” due to its slow and adverse effect on various biological pathways in humans, particularly among children, in whom it leads to delayed development, stunted growth, liver damage, and liver cancer. Unfortunately, the unpredictable behavior of the fungus as well as climatic conditions pose serious challenges in precise phenotyping, genetic prediction and genetic improvement, leaving the complete onus of preventing aflatoxin contamination in crops on post-harvest management. Equipping popular crop varieties with genetic resistance to aflatoxin is key to effective lowering of infection in farmer’s fields. A combination of genetic resistance for in vitro seed colonization (IVSC), pre-harvest aflatoxin contamination (PAC) and aflatoxin production together with pre- and post-harvest management may provide a sustainable solution to aflatoxin contamination. In this context, modern “omics” approaches, including next-generation genomics technologies, can provide improved and decisive information and genetic solutions. Preventing contamination will not only drastically boost the consumption and trade of the crops and products across nations/regions, but more importantly, stave off deleterious health problems among consumers across the globe.
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Zdebska, Ewa, Beata Burzynska, Ewa Mendek-Czajkowska, Malgorzata Maciag, Angelika Krawcewicz, Urszula Mokras, Anna Adamowicz-Salach, and Jerzy Koscielak. "Molecular Analysis of β-Thalassemia Cases in Poland." Blood 106, no. 11 (November 16, 2005): 3834. http://dx.doi.org/10.1182/blood.v106.11.3834.3834.
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Abstract β-thalassemia is a heterogenous, inherited disease resulting from reduced or absent synthesis of β-globin chain of haemoglobin. This disorder is very common in the Mediterranean, Middle Eastern, African and South-East Asian populations. The aim of the present investigation was to verify a common view that thalassemia in Poland is a very rare disease. 600 patients (270 men and 330 women), aged 2–85 years, with microcytosis and no evidence of iron deficiency, were examined for β-thalassemia. Hemoglobin A2 was increased in 106 patients. In 48 patients there was also an elevation of hemoglobulin F and in 42 patients of serum bilirubin. All 106 patients were examined for 8 common Mediterranean mutations. 7 different mutations were detected in 46 heterozygous patients (number of patients wit a particular mutations are in square brackets): IVS1-6(T>C) [15]; IVS2-745(C>G)[14]; IVS2-1(G>A) [10]; IVS1-1(G>A) [2]; CD6-A [2]; CD39(C>T) [2]; IVS1-110(G>A) [1]. We also discuss the effect of these mutations on the expression level of the β-globin gene. Frequencies of individual mutations in Poland were different from those encountered in Mediterranean and some Centrak European countries. We also detect two novel mutations: IVS-1-1(G>A) G^GTTGGT>AGATTGGT and 5′UTR; +33(C>T). The first novel mutation significantly decreased the mRNA level of the β-globin gene. The second mutation seems to be silent and does not affect β-globin synthesis. In this case, this particular mutation occurs with IVS-1-6(G>C) mutation in compound the heterozygotes stage.
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Jiang, Xiaobing. "Intravertebral Vacuum Cleft and Its Varied Locations within Osteoporotic Vertebral Compression Fractures: Effect on Therapeutic Efficacy." september 2017 6, no. 20;6 (August 12, 2017): E979—E986. http://dx.doi.org/10.36076/ppj.20.5.e979.
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Background: Previous studies have reported a high incidence of re-collapse of the augmented vertebrae after percutaneous vertebral augmentation (PVA) for osteoporotic vertebral compression fractures (OVCFs) with intravertebral vacuum cleft (IVC) during long-term followup. Previous IVC might be considered an important predisposing factor for re-collapse, but the prior studies could not find a significant correlation. Objective: To determine the incidence and distribution characteristics of IVCs and to further assess IVCs in their varied locations. To assess the long-term therapeutic efficacy of PVA for OVCFs with IVC. Study Design: A retrospective cohort study. Setting: Department of spinal surgery, an affiliated hospital of a medical university. Methods: A retrospective review was performed on 594 patients who underwent PVA to treat OVCFs from January 2010 to December 2013. Eighty-two patients with the IVC sign were enrolled in the study. The follow-up period was a minimum of 2 years. The difference between IVC and non-IVC patients was compared. Comparisons of the radiological and clinical findings at varied IVC locations were made pre-operatively and post-operatively (immediate, at one year, and at 2 years). Results: IVC incidence correlated with older patient age and severe demineralization. Other baseline parameters showed no significant differences. The rate of cement leakage and vertebral fracture was significantly lower in the IVC groups than in the non-IVC groups intraoperatively. There was no significant difference in the incidence of cement leakage or adjacent vertebral fractures between the 3 IVC groups. In the immediate postoperative period, all patients benefited from significant improvement in vertebral body height and kyphotic angle correction. However, significant re-collapse was observed at the 2-year post-operative followup for the IVC patients when compared to the non-IVC patients. Among the 3 IVC groups, the most severe re-collapse was observed with inferior endplate IVCs. Superior endplate IVCs and IVCs extending to both endplates demonstrated only mild re-collapse at the 2-year follow-up. Limitation: Due to the infrequency of this process, the number of patients with IVCs was small. Conclusion: PVA treatment was initially effective in all patients with OVCFs. However, significant re-collapse of the augmented vertebrae with IVCs, especially those with inferior endplate IVCs, was found with long-term follow-up.
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Singh, Shweta, Gourdas Choudhuri, and Sarita Agarwal. "Frequency of CFTR, SPINK1, and Cathepsin B Gene Mutation in North Indian Population: Connections between Genetics and Clinical Data." Scientific World Journal 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/763195.
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Objectives. Genetic mutations and polymorphisms have been correlated with chronic pancreatitis (CP). This study aims to investigate the association of genetic variants of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) genes and Cathepsin B gene polymorphisms with CP and to associate genetic backgrounds with clinical phenotypes.Methods. 150 CP patients and 150 normal controls were enrolled consecutively. We analyzed SPINK-1 N34S and IVS3+2T>C gene mutations by PCR-restriction-fragment length polymorphism (RFLP). The identification of DF508, G551D, G542X, R117H, and W1282X mutations was carried out by ARMS-PCR. S549N mutation, IVS8 polyTn polymorphism, and Cathepsin B Lec26Val were analysed by PCR-RFLP, nested PCR, and PCR-RFLP plus sequencing, respectively.Results. We found a significant association of SPINK1 (N34S) gene polymorphism. IVS1−37T>C polymorphism shows linkage with 101A>G. 300 chromosomes belonging to the CFTR subgroup exhibited minor allele frequency of 0.04, 0.03, 0.03, 0.013, 0.006, and 0.02 for DF508, G452X, G551D, S549N, R117H, and IVS8 T5, respectively. Except for R117H and IVS8 T5 polymorphisms, all other mutations showed significant variation.Conclusion. Analysis of potential susceptibility variants is needed to support nature of the genes and environment in pancreatitis. This data may help establish genetic screening and prenatal setup for Indian population.
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Nguyen, Cong-Trang, Thanh Long Duong, Minh Quan Duong, and Duc Tung Le. "Chattering-Free Single-Phase Robustness Sliding Mode Controller for Mismatched Uncertain Interconnected Systems with Unknown Time-Varying Delays." Energies 13, no. 1 (January 6, 2020): 282. http://dx.doi.org/10.3390/en13010282.
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Variable structure control with sliding mode can provide good control performance and excellent robustness. Unfortunately, the chattering phenomenon investigated due to discontinuous switching gain restricting their applications. In this paper, a chattering free improved variable structure control (IVSC) for a class of mismatched uncertain interconnected systems with an unknown time-varying delay is proposed. A sliding function is first established to eliminate the reaching phase in traditional variable structure control (TVSC). Next, a new reduced-order sliding mode estimator (ROSME) without time-varying delay is constructed to estimate all unmeasurable state variables of plants. Then, based on the Moore-Penrose inverse approach, a decentralized single-phase robustness sliding mode controller (DSPRSMC) is synthesized, which is independent of time delays. A DSPRSMC solves a complex interconnection problem with an unknown time-varying delay term and drives the system’s trajectories onto a switching surface from the initial time instance. Particularly, by applying the well-known Barbalat’s lemma, the chattering phenomenon in control input is alleviated. Moreover, a sufficient condition is established by using an appropriate Lyapunov theory and linear matrix inequality (LMI) method such that a sliding mode dynamics is asymptotically stable from the beginning time. Finally, a developed method is validated by numerical example with computer simulations.
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Raslanas, Saulius. "PECULIARITIES OF MORGAGE VALUATION." Technological and Economic Development of Economy 11, no. 2 (June 30, 2005): 123–33. http://dx.doi.org/10.3846/13928619.2005.9637691.
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Valuation for mortgage purposes is a very important part of the work of a surveyor in general practice. The property is valued at the date of inspection, but bearing in the future ‐ will the value be maintained and easily realizable. This work considers the important aspects of the approach to such valuation and the factors witch the valuer should take into account. In UK open market valuers use value as the basics of mortgage valuation, but possible diminution of value cannot be ignored. A valuer must inform the lender about special circumstances and the risk and duty of care, of the prospective purchase, which may base his decision to purchase on the valuer's report. In Germany the lending value is always established on the basis of real value (cost approach and income approach) (.dual pillar principle.), with both values being calculated independently of each other (control function). Depending on the type of property, the Mortgage Lending Value (MLV) will as a rule be derived through cost‐ or the income approach. Mortgage Lending Value, provaided by the European Group of Valuers. Associations (TEGoVA) and the International Valuation Standards Committee (IVSC) are not strongly defined and it is necessary to rate criteria for the determination of the risk profile of property.
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Brito, Vinicius Nahime, Berenice Bilharinho Mendonca, Laura M. F. F. Guilhoto, Karina Cocco Monteiro Freitas, Ivo J. Prado Arnhold, and Ana Claudia Latronico. "Allelic Variants of the γ-Aminobutyric Acid-A Receptor α1-Subunit Gene (GABRA1) Are Not Associated with Idiopathic Gonadotropin-Dependent Precocious Puberty in Girls with and without Electroencephalographic Abnormalities." Journal of Clinical Endocrinology & Metabolism 91, no. 6 (June 1, 2006): 2432–36. http://dx.doi.org/10.1210/jc.2005-2657.
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Abstract Context: γ-Aminobutyric acid (GABA) is a dominant inhibitory neurotransmitter involved in the modulation of brain electric activity and puberty onset in primates. GABA inhibitory effects on GnRH neurons are mainly mediated by GABA-A receptor α1-subunit. Objective: The objective of this study was to investigate functional mutations or polymorphisms of the GABA-A receptor α1-subunit gene (GABRA1) in girls with idiopathic gonadotropin-dependent precocious puberty (GDPP) with and without electroencephalographic (EEG) abnormalities. Design: The entire coding region of GABRA1 was sequenced in all patients. Two known GABRA1 polymorphisms were investigated by GeneScan software analysis or enzymatic restriction. Seventy-three normal women were used as controls for genetic study. EEG tracings were recorded in 23 girls with GDPP and 17 girls with adequate pubertal development. Setting: The study was performed at a university hospital. Patients: Thirty-one girls from 28 unrelated families with idiopathic GDPP were studied. Results: Automatic sequencing revealed no functional mutations in girls with GDPP. Seven different GABRA1 polymorphisms, including two exonic (156T>C and 1323G>A) and five intronic [IVS2–712(GT)n, IVS3+12A>T, IVS8+45T>G, IVS9+76A>G, and IVS10+15G>A], were found in GDPP girls and controls. Abnormal EEG tracings were found in 26% of 23 girls with GDPP, two of them with epilepsy. The genotype and allele frequencies of the GABRA1 polymorphisms were not statistically different between unrelated GDPP girls and controls or between GDPP girls with or without EEG abnormalities. Conclusions: GABRA1 functional mutations or polymorphisms are not associated with the intrinsic mechanism of GDPP in girls with and without EEG abnormalities.
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Miller, Wayne L., Kanti Pabbaraju, and Kenneth E. Sanderson. "Fragmentation of 23S rRNA in Strains of Proteus andProvidencia Results from Intervening Sequences in therrn (rRNA) Genes." Journal of Bacteriology 182, no. 4 (February 15, 2000): 1109–17. http://dx.doi.org/10.1128/jb.182.4.1109-1117.2000.
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ABSTRACT Intervening sequences (IVSs) were originally identified in therrl genes for 23S rRNA (rrl genes, for large ribosomal subunit, part of rrn operon encoding rRNA) ofSalmonella enterica serovars Typhimurium LT2 and Arizonae. These sequences are transcribed but later removed during RNase III processing of the rRNA, resulting in fragmentation of the 23S species; IVSs are uncommon, but have been reported in at least 10 bacterial genera. Through PCR amplification of IVS-containing regions of therrl genes we showed that most Proteus andProvidencia strains contain IVSs similar to those of serovar Typhimurium in distribution and location in rrlgenes. By extraction and Northern blotting of rRNA, we also found that these IVSs result in rRNA fragmentation. We report the first finding of two very different sizes of IVS (113 bp and 183 to 187 bp) in differentrrl genes in the same strain, in helix 25 ofProteus and Providencia spp.; IVSs from helix 45 are 113 to 123 bp in size. Analysis of IVS sequence and postulated secondary structure reveals striking similarities ofProteus and Providencia IVSs to those of serovar Typhimurium, with the stems of the smaller IVSs from helix 25 being similar to those of Salmonella helix 25 IVSs and with both the stem and the central loop domain of helix 45 IVSs being similar. Thus, IVSs of related sequences are widely distributed throughout the Enterobacteriaceae, inSalmonella, Yersinia, Proteus, andProvidencia spp., but we did not find them inEscherichia coli, Citrobacter,Enterobacter, Klebsiella, orMorganella spp.; the sporadic distribution of IVSs of related sequence indicates that lateral genetic transfer has occurred.
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Attanasio, Catia, Armelle David, and Marguerite Neerman-Arbez. "Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA)." Blood 101, no. 5 (March 1, 2003): 1851–56. http://dx.doi.org/10.1182/blood-2002-03-0853.
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Congenital afibrinogenemia (Mendelian Inheritance in Man #202400) is a rare, autosomal recessive disorder characterized by the complete absence of circulating fibrinogen. Our recent studies on the molecular basis of the disease showed that the most common genetic defect is a donor splice mutation in fibrinogen alpha gene (FGA)intron 4, IVS4+1G>T. Two other FGA donor splice mutations, in intron 1 (IVS1+3A>G) and intron 3 (IVS3+1_+4delGTAA), were identified in afibrinogenemia patients. Because it was impossible to directly study the effect of these mutations on mRNA splicing in patient hepatocytes, we used a transfected cell approach, which previously allowed us to show that the common IVS4 mutation causes afibrinogenemia due to the activation of multiple cryptic donor splice sites. In this study, analysis of the IVS3delGTAA mutation showed exon 3 skipping in 99% of transcripts and exons 2 and 3 skipping in 1% of transcripts. The different outcomes of these donor splice mutations appear to follow the model proposed in a study of fibrillar collagen genes, where donor splice mutations occurring in a rapidly spliced intron with respect to upstream introns lead in most cases to exon skipping, while mutations in later-spliced introns lead to intron inclusion or cryptic splice-site utilization. Indeed, we found that inFGA intron 3 was preferentially spliced first, followed by intron 2, intron 4, and intron 1.
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Juhl-Olsen, P., C. Frederiksen, and E. Sloth. "Ultrasound Assessment of Inferior Vena Cava Collapsibility Is Not a Valid Measure of Preload Changes During Triggered Positive Pressure Ventilation: A Controlled Cross-Over Study." Ultraschall in der Medizin - European Journal of Ultrasound 33, no. 02 (December 16, 2011): 152–59. http://dx.doi.org/10.1055/s-0031-1281832.
Full textAbstract:
Zusammenfassung Ziel: Die respiratorischen Veränderungen im Durchmesser der Vena cava inferior (IVC) wurden durch Messung des Volumenstatus und der Vorlastreagilibität während der Spontanatmung und maschinellen Beatmung bewertet. Allerdings erhalten viele Intensivpatienten eine getriggerte Überdruckbeatmung (PPV). Bei dieser Anwendung gibt es keinen Beweis dafür, dass die „Collapsibility“ der IVC (IVCc) als Ersatz für die Vorlast dient. Unser Ziel war es zu klären, welche Auswirkungen die stufenweise Erhöhung der getriggerten PPV und die unterschiedlichen Vorlast-Bedingungen auf die IVCc haben. Material und Methoden: 10 gesunde Freiwillige wurden an ein Beatmungsgerät mit festsitzender Maske angeschlossen und nach der Basismessung drei verschiedenen Stufen des positiven endexspiratorischen Drucks (PEEP) und der Druckunterstützung (Pressure support, PS) ausgesetzt. Alle Einstellungen des Beatmungsgeräts wurden bei neutraler Vorlast (Horizontalposition), niedriger Vorlast (reverse Trendelenburg-Lage) und hoher Vorlast (Trendelenburg-Lage mit intravenöser Flüssigkeits-Bolusinjektion) durchgeführt. Bei jeder Einstellung des Beatmungsgeräts wurde die IVC während mindestens einem respiratorischen Zyklus durch drei häufig benutzte Ultraschallmethoden dargestellt, darunter der sagittale M-Modus und die 2D-Echokardiografie sowohl in Sagittal- als auch in Transversalansicht. Ergebnisse: Bei ansteigender PS verminderte sich die IVCc (p = 0,01) in der reversen Trendelenburg-Lage, steigender PEEP verursachte eine höhere IVCc in der Trendelenburg-Lage (p = 0,02). In Horizontalposition wurden keine signifikanten Auswirkungen einer steigenden PS, PEEP oder einer Kombination aus beiden beobachtet. Insgesamt zeigte die ANOVA Analyse, dass die IVCc nicht unabhängig von der Vorlast ist. Unter PPV war die IVCc bei neutraler Vorlast mit den meisten Einstellungen des Beatmungsgeräts am höchsten, die IVCc war bei niedriger Vorlast am niedrigsten, während eine hohe Vorlast in der Regel die ICVc zwischen neutraler und hoher Vorlast ermöglichte. Darüber hinaus überschätzte der sagittale M-Mode und die transversale 2D-Echokardiografie die IVCc im Vergleich zur sagittalen 2D-Echokardiografie. Schlussfolgerung: Die erhobenen Ergebnisse dieser Studie zeigen, dass die IVCc nicht als gültiger Parameter für den Vorlaststatus während der PPV angesehen werden kann. Das könnte durch die systematischen Veränderungen der anderen IVCc-Einflussgrößen erklärt werden. Der Vergleich der Methoden ermutigt dazu, die sagittale 2D-Echokardiografie zur dynamischen Darstellung der IVC einzusetzen. Im Vergleich zur sagittalen 2D-Echokardiografie überschätzen der sagittale M-Mode und die transversale 2D-Echokardiografie die IVCc.
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Chan, Kamfai, William G. Miller, Robert E. Mandrell, and Sophia Kathariou. "The Absence of Intervening Sequences in 23S rRNA Genes of Campylobacter coli Isolates from Turkeys Is a Unique Attribute of a Cluster of Related Strains Which Also Lack Resistance to Erythromycin." Applied and Environmental Microbiology 73, no. 4 (December 22, 2006): 1208–14. http://dx.doi.org/10.1128/aem.01995-06.
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ABSTRACT Certain Campylobacter strains harbor a transcribed intervening sequence (IVS) in their 23S rRNA genes. Following transcription, the IVS is excised, leading to fragmentation of the 23S rRNA. The origin and possible functions of the IVS are unknown. Furthermore, the distribution of IVS-harboring strains within Campylobacter populations is poorly understood. In this study, 104 strains of Campylobacter coli from turkeys, representing 27 different multilocus sequence typing-based sequence types (STs), were characterized in terms of IVS content and erythromycin susceptibility. Sixty-nine strains harbored IVSs in all three 23S rRNA genes, whereas the other 35 strains lacked IVSs from at least one of the genes. The STs of the latter strains belonged to an unusual cluster of C. coli STs (cluster II), earlier found primarily in turkey strains and characterized by the presence of the C. jejuni aspA103 allele. The majority (66/69) of strains harboring IVSs in all three 23S rRNA genes were resistant to erythromycin, whereas none of the 35 strains with at least one IVS-free 23S rRNA gene were resistant. Cluster II strains could be transformed to erythromycin resistance with genomic DNA from C. coli that harbored IVS and the A2075G transition in the 23S rRNA gene, associated with resistance to erythromycin in Campylobacter. Erythromycin-resistant transformants harbored both the A2075 transition and IVS. The findings suggest that the absence of IVS in C. coli from turkeys is characteristic of a unique clonal group of erythromycin-susceptible strains and that IVS can be acquired by these strains via natural transformation to erythromycin resistance.
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Pineda, Danielle, Neil Moudgill, Joshua Eisenberg, Paul DiMuzio, and Atul Rao. "An interesting anatomic variant of inferior vena cava duplication: case report and review of the literature." Vascular 21, no. 3 (May 13, 2013): 163–67. http://dx.doi.org/10.1177/1708538113478731.
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Congenital anomalies of the inferior vena cava (IVC) occur in roughly 4% of the population. We report an interesting case of an atypical variant of duplicated IVC. A 20-year-old man presented with orthopedic injuries and intracranial hemorrhage following a motorcycle accident. He was taken to the fluoroscopy suite for IVC filter placement; duplication of the IVC was noted. The right and left iliac veins shared a normal confluence but two IVCs drained independently into renal veins before reuniting into a single structure. Both IVC filters were placed via a single puncture in the groin. We performed a search of the PubMed database using ‘inferior vena cava duplication’ and reviewed common anomalies of the IVC. Several variants of duplicated IVC exist; the most common of which is two distinct IVCs that arise from each iliac vein without a normal confluence. Our patient had a unique anomaly which allowed filter placements from a single puncture.
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Chen, P. R., L. D. Spate, W. G. Spollen, R. F. Cecil, M. S. Samuel, and R. S. Prather. "4 Aryl hydrocarbon receptor targets are upregulated in porcine blastocyst-stage embryos that were cultured invitro: A transcriptional analysis." Reproduction, Fertility and Development 33, no. 2 (2021): 109. http://dx.doi.org/10.1071/rdv33n2ab4.
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Invitro-produced (IVP) porcine embryos are developmentally delayed compared with those derived invivo. Thus, efforts have been made to modify the current medium for IVP of porcine embryos in an attempt to shift the abundance of target transcripts towards the invivo level. The objective of the current study was to identify differences in mRNA abundance that may account for reduced developmental competence in IVP embryos and to determine whether alterations to maturation and culture media directed the transcriptional profiles of IVP embryos towards an invivo state. Following AI of gilts, an oviduct and tip of the uterine horn were flushed on Day 2 to recover 4-cell stage embryos; these were cultured for 4 days in MU3, generating IVM and invitro-cultured (IVC) blastocyst-stage embryos. On Day 6, the gilts were killed, and the contralateral horns were flushed to obtain invivo-derived (IVV) blastocyst-stage embryos. The third group of blastocyst-stage embryos, referred to as invitro-matured and cultured (IVMC), were created by aspirating cumulus–oocyte complexes from slaughterhouse-derived ovaries, maturing and fertilizing invitro, and culturing for 6 days in MU3. Total RNA was extracted from pools of 10 blastocyst-stage embryos with 3 replicates per group. First- and second-strand cDNA was synthesised and sequenced by using the Illumina platform (Illumina Inc.). After removal of adapters and reads that mapped to porcine rRNA genes and the PhiX genome, reads were mapped to the Sus scrofa genome by using STAR (version 2.7.1a) with default options. Pairwise comparisons were performed to test for differential expression of genes by using the Bioconductor package DESEqn 2. Transcripts were differentially abundant (false discovery rate <0.05) between IVV and IVC embryos (2,450), between IVV and IVMC embryos (3,045), and between IVC and IVMC embryos (262). Pathways related to cell cycle were downregulated in IVC and IVMC compared with IVV embryos, and pathways related to amino acid transport in metabolism were upregulated in IVC and IVMC compared with IVV embryos. Of particular interest, message for cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was only present in the IVC (956 reads) and IVMC (381 reads) embryos but not in the IVV embryos (0 reads). The aryl hydrocarbon receptor (AHR) promotes transcription of CYP1A1, which encodes a monooxygenase involved in xenobiotic metabolism. Moreover, abundance of 12 other AHR targets was increased in IVC and IVMC embryos (false discovery rate <0.05) compared with IVV embryos. Thus, production of porcine embryos invitro may activate AHR, resulting in altered transcriptional profiles and reduced competence. This research was funded by USDA-NIFA (2019-67011-29543).
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Chen, P. R., L. D. Spate, W. G. Spollen, R. F. Cecil, M. S. Samuel, and R. S. Prather. "4 Aryl hydrocarbon receptor targets are upregulated in porcine blastocyst-stage embryos that were cultured invitro: A transcriptional analysis." Reproduction, Fertility and Development 33, no. 2 (2021): 109. http://dx.doi.org/10.1071/rdv33n2ab4.
Full textAbstract:
Invitro-produced (IVP) porcine embryos are developmentally delayed compared with those derived invivo. Thus, efforts have been made to modify the current medium for IVP of porcine embryos in an attempt to shift the abundance of target transcripts towards the invivo level. The objective of the current study was to identify differences in mRNA abundance that may account for reduced developmental competence in IVP embryos and to determine whether alterations to maturation and culture media directed the transcriptional profiles of IVP embryos towards an invivo state. Following AI of gilts, an oviduct and tip of the uterine horn were flushed on Day 2 to recover 4-cell stage embryos; these were cultured for 4 days in MU3, generating IVM and invitro-cultured (IVC) blastocyst-stage embryos. On Day 6, the gilts were killed, and the contralateral horns were flushed to obtain invivo-derived (IVV) blastocyst-stage embryos. The third group of blastocyst-stage embryos, referred to as invitro-matured and cultured (IVMC), were created by aspirating cumulus–oocyte complexes from slaughterhouse-derived ovaries, maturing and fertilizing invitro, and culturing for 6 days in MU3. Total RNA was extracted from pools of 10 blastocyst-stage embryos with 3 replicates per group. First- and second-strand cDNA was synthesised and sequenced by using the Illumina platform (Illumina Inc.). After removal of adapters and reads that mapped to porcine rRNA genes and the PhiX genome, reads were mapped to the Sus scrofa genome by using STAR (version 2.7.1a) with default options. Pairwise comparisons were performed to test for differential expression of genes by using the Bioconductor package DESEqn 2. Transcripts were differentially abundant (false discovery rate <0.05) between IVV and IVC embryos (2,450), between IVV and IVMC embryos (3,045), and between IVC and IVMC embryos (262). Pathways related to cell cycle were downregulated in IVC and IVMC compared with IVV embryos, and pathways related to amino acid transport in metabolism were upregulated in IVC and IVMC compared with IVV embryos. Of particular interest, message for cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was only present in the IVC (956 reads) and IVMC (381 reads) embryos but not in the IVV embryos (0 reads). The aryl hydrocarbon receptor (AHR) promotes transcription of CYP1A1, which encodes a monooxygenase involved in xenobiotic metabolism. Moreover, abundance of 12 other AHR targets was increased in IVC and IVMC embryos (false discovery rate <0.05) compared with IVV embryos. Thus, production of porcine embryos invitro may activate AHR, resulting in altered transcriptional profiles and reduced competence. This research was funded by USDA-NIFA (2019-67011-29543).
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Konoki, Keiichi, Daniel G. Baden, Todd Scheuer, and William A. Catterall. "Molecular Determinants of Brevetoxin Binding to Voltage-Gated Sodium Channels." Toxins 11, no. 9 (September 3, 2019): 513. http://dx.doi.org/10.3390/toxins11090513.
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Brevetoxins are produced by dinoflagellates such as Karenia brevis in warm-water red tides and cause neurotoxic shellfish poisoning. They bind to voltage-gated sodium channels at neurotoxin receptor 5, making the channels more active by shifting the voltage-dependence of activation to more negative potentials and by slowing the inactivation process. Previous work using photoaffinity labeling identified binding to the IS6 and IVS5 transmembrane segments of the channel α subunit. We used alanine-scanning mutagenesis to identify molecular determinants for brevetoxin binding in these regions as well as adjacent regions IVS5-SS1 and IVS6. Most of the mutant channels containing single alanine substitutions expressed functional protein in tsA-201 cells and bound to the radioligand [42-3H]-PbTx3. Binding affinity for the great majority of mutant channels was indistinguishable from wild type. However, transmembrane segments IS6, IVS5 and IVS6 each contained 2 to 4 amino acid positions where alanine substitution resulted in a 2–3-fold reduction in brevetoxin affinity, and additional mutations caused a similar increase in brevetoxin affinity. These findings are consistent with a model in which brevetoxin binds to a protein cleft comprising transmembrane segments IS6, IVS5 and IVS6 and makes multiple distributed interactions with these α helices. Determination of brevetoxin affinity for Nav1.2, Nav1.4 and Nav1.5 channels showed that Nav1.5 channels had a characteristic 5-fold reduction in affinity for brevetoxin relative to the other channel isoforms, suggesting the interaction with sodium channels is specific despite the distributed binding determinants.
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Bakos, Z., K. Vörös, and Taina Järvinen. "Two-dimensional and M-mode echocardiographic measurements of cardiac dimensions in healthy Standardbred trotters." Acta Veterinaria Hungarica 50, no. 3 (July 1, 2002): 273–82. http://dx.doi.org/10.1556/avet.50.2002.3.3.
Full textAbstract:
The aim of the study was to establish normal echocardiographic values of healthy Standardbred trotters not published previously. Twenty-three clinically normal horses weighing between 350 and 490 kg were examined in the same manner: first a thorough physical and then detailed echocardiographic examination were performed. Standardised two-dimensional (2D) and guided M-mode echocardiographic imaging techniques were used to measure interventricular septal thickness (IVS), left ventricular internal diameter (LVID), left ventricular wall thickness (LVW), left atrial internal diameter (LAID) in end-systole (s) and end-diastole (d) and aortic diameter (AOD) in end-diastole. Mean, range and standard deviation of the different parameters were calculated. The mean values (in centimetres) were as follow (2D/M-mode): IVSs: 4.6/4.7; IVSd: 3.1/3.0; LVIDs: 7.0/7.0; LVIDd: 10.7/10.7; LVWs: 3.9/3.9; LVWd: 2.7/2.7; LAIDs: 10.4/-; LAIDd: 11.3/-; AODd: 7.2/-. Results of two-dimensional and M-mode measurements were compared to each other and to normal values obtained from other breeds.
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Winters, Chelsea M., Ly Q. Hong-Brown, and Hui-Ling Chiang. "Intracellular vesicle clusters are organelles that synthesize extracellular vesicle–associated cargo proteins in yeast." Journal of Biological Chemistry 295, no. 9 (January 23, 2020): 2650–63. http://dx.doi.org/10.1074/jbc.ra119.008612.
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Extracellular vesicles (EVs) play important roles in cell-cell communication. In budding yeast (Saccharomyces cerevisiae), EVs function as carriers to transport cargo proteins into the periplasm for storage during glucose starvation. However, intracellular organelles that synthesize these EV-associated cargo proteins have not been identified. Here, we investigated whether cytoplasmic organelles—called intracellular vesicle clusters (IVCs)—serve as sites for the synthesis of proteins targeted for secretion as EV-associated proteins. Using proteomics, we identified 377 IVC-associated proteins in yeast cells grown under steady-state low-glucose conditions, with the largest group being involved in protein translation. Isolated IVCs exhibited protein synthesis activities that required initiation and elongation factors. We have also identified 431 newly synthesized proteins on isolated IVCs. Expression of 103Q-GFP, a foreign protein with a long polyglutamine extension, resulted in distribution of this protein as large puncta that co-localized with IVC markers, including fructose-1,6-bisphosphatase (FBPase) and the vacuole import and degradation protein Vid24p. We did not observe this pattern in cycloheximide-treated cells or in cells lacking VID genes, required for IVC formation. The induction of 103Q-GFP on IVCs adversely affected total protein synthesis in intact cells and on isolated IVCs. This expression also decreased levels of EV-associated cargo proteins in the extracellular fraction without affecting the number of secreted EVs. Our results provide important insights into the functions of IVCs as sites for the synthesis of EV-associated proteins targeted for secretion to the periplasm.
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Gupta, Deepesh, Kusum Devpura, and Kamlesh Kumar Agrawal. "Comparison of the inferior vena cava index and inferior vena cava collapsibility index obtained by ultrasound as a measure of body fluid volume status in children with nephrotic syndrome." International Journal of Contemporary Pediatrics 6, no. 3 (April 30, 2019): 1298. http://dx.doi.org/10.18203/2349-3291.ijcp20192032.
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Background: There is triad of hypoalbuminemia, edema, and hyperlipidemia in nephrotic syndrome patients. Management of nephrotic syndrome includes general measures like fluid restriction, emergency albumin transfusions and diuretics that provide symptomatic relief till steroids act. These measures require an assessment of body fluid volume to avoid circulatory failure which is very difficult in these patients because of edema. The objective of the study was to measure and compare the Inferior Vena Cava (IVC) Index and Inferior Vena Cava Collapsibility (IVCC) Index by ultrasound as a measure of body fluid volume status in children with nephrotic syndrome.Methods: The present observational study was conducted in all children of age more than 1 year up to 18 year. There were two groups; group 1 was nephrotic syndrome patients-Initial episode or in relapse and group 2 (Control) was age and sex-matched non-nephrotic children. IVC index and IVCC index were measured and compared in both the groups.Results: Mean value of minimum diameter of IVC during inspiration in cases was 5.91±1.60 mm as compared to 4.53±0.94 mm in controls which was significantly higher in case group {P ˂0.0001}. Mean value of IVC index in cases was 0.88±0.20 cm/m2 as compared to 0.93±0.19 cm/m2 in controls which was non-significant. Mean value of IVCC index in cases (35.61±13.68) was significantly less as compared to controls (52.23±2.01) {P ˂0.0001}.Conclusions: The present study concluded that IVCC index is better indicator of body fluid volume status in nephrotic patients as compare to IVC index.
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Bernig, Toralf, Laurie Burdette, Thomas Lehrnbecher, Ulrike B. Graubner, Monique L. den Boer, Rob Pieters, Gritta E. Janka-Schaub, and Stephen J. Chanock. "Germ-Line Genetic Variations in TP53 and Risk for Pediatric Acute Lymphoblastic Leukemia." Blood 104, no. 11 (November 16, 2004): 1890. http://dx.doi.org/10.1182/blood.v104.11.1890.1890.
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Abstract The tumor suppressor p53 plays an essential role in the prevention of tumor development by its ability to respond to stress signals, resulting in the inhibition of cell growth, via cell-cycle arrest or induction of apoptosis. p53 also contributes to the repair of genotoxic DNA damages and is involved in cellular senescence. Previous studies have shown that both germ-line and somatic mutations in the TP53 gene, which encodes p53, can occur in a wide spectrum of cancers, including acute lymphoblastic leukemia, ALL. Recently, we characterized the common germ-line genetic variation across TP53 by extensive re-sequence analysis (http://snp500cancer.nci.nih.gov). Patients and Methods: We conducted a genetic association study in childhood ALL to investigate the possible contribution of common single nucleotide polymorphisms, SNPs, and the common haplotypes on which they reside. For TP53, we analyzed haplotype-tagging SNPs, which are estimated to capture greater than 95% of common haplotypes across the gene (IVS2+38C, Ex4+119 (R72P), IVS4-91, Ex6-34 (R213R), IVS6+62, IVS6-36 and 1846bp 3′ of STP). Cases of ALL (n = 513) were drawn from anonymized samples from the German co-operative therapy study (COALL-06-97) and 751 healthy anonymized blood donor controls collected from regional blood banks in Germany. Genotype analysis was performed by validated Taqman assays posted on the SNP500cancer website. Haplotypes were deduced by maximization-estimation analysis of unphased genotypes using PHASEv2.0.1 (http://www.stat.washington.edu/stephens/software.html). Results: The single locus analysis revealed an increased risk for ALL for four of the seven SNPs individually: C allele at IVS2+38C (304/982 in patients vs. 399/1476 in controls, OR 1.21 95% CI 1.01 – 1.45), G allele at IVS4-91 (150/988 vs. 168/1456, OR 1.37 95% CI 1.08 – 1.75), A allele at Ex6-34 (R213R) (164/996 vs. 178/1450, OR 1.41 95% CI 1.11 – 1.78) and T allele at 1846bp 3′ of STP (185/990 vs. 203/1420, OR 1.38 95% CI 1.10 – 1.72). Individuals homozygous AA at IVS6+62 (16/350 vs. 9/556, OR 2.82, 95% CI 1.16 – 6.99) or TT at 1846bp 3′ of STP (24/334 vs. 15/522 OR 2.50, 955 CI 1.24 – 5.09) showed further risk for disease. The non-synonymous coding SNP at Ex4+119 (R72P) did not show any association with ALL. The distribution of the inferred haplotypes differed significantly between cases and controls (global haplotype test p = 0.02). Children carrying the haplotype CCGAAGT have an increased risk for ALL (138/611 vs. 155/972, OR 1.42, 95% CI 1.09 −1.83) in reference to the most common haplotype GGAAGGC. Conclusions: Our data suggest that susceptibility to pediatric ALL could be associated with at least one copy of an “at risk” haplotype. The study results imply that germ-line genetic variation in TP53, a key tumor suppressor gene, could contribute to susceptibility to childhood ALL. Additional studies are required to confirm our findings and to characterize the functional elements in the at-risk haplotypes.
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Silva, J. R., G. P. Meirelles, E. M. Busato, B. C. Brüler, R. G. D’O C. Vilani, R. L. Guedes, M. G. Sousa, and P. T. Dornbusch. "Evaluation of echocardiographic variables of morphometry and function in horses submitted to minimally invasive partial pericardiotomy." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 72, no. 5 (September 2020): 1577–85. http://dx.doi.org/10.1590/1678-4162-11806.
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ABSTRACT This study aimed to evaluate the impact of minimally invasive partial pericardiotomy on echocardiographic variables of morphometry and function in healthy horses. Minimally invasive pericardiotomy was performed in six healthy horses. Echocardiographic evaluation was executed in different moments: prior to the surgical procedure (M0); 24 hours post procedure (M1); 72 hours post procedure (M2) and 28 days post procedure (M3). The following variables were measured: Right ventricular internal diameter in diastole and systole (RVd and RVs), interventricular septum thickness in diastole and systole (IVSd and IVSs), left ventricular internal diameter in diastole and systole (LVd and LVs), left ventricular free wall thickness in diastole and systole (LVFWd and LVFWs), aortic root diameter (Ao) and left atrial diameter (LA). From this data, the following variables were calculated: fractional shortening (FS%), fractional thickening of the interventricular septum (IVS%), fractional thickening of the left ventricular free wall (LVFW%) and the relationship between left atrial and aortic diameters (LA/Ao). After 28 days, a new thoracoscopy was performed for inspection of the thoracic cavity. In M1 and M2 ECO evaluations, a statistically significant change in LVFW and a decrease in RVd, LVd, LVFWs, LA, LVs, FS% and IVS was documented. Pericardiotomy is a promising technique in horses, with minor postoperative complication. The variations in the echocardiographic parameters were transient and did not cause hemodynamic damage to the animals.
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Tuluc, Petronel, Bruno Benedetti, Pierre Coste de Bagneaux, Manfred Grabner, and Bernhard E. Flucher. "Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels." Journal of General Physiology 147, no. 6 (May 16, 2016): 437–49. http://dx.doi.org/10.1085/jgp.201611568.
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Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms within the IV and I VSDs, respectively.
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Spena, Silvia, Stefano Duga, Rosanna Asselta, Massimo Malcovati, Flora Peyvandi, and Maria Luisa Tenchini. "Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bβ-chain gene causing activation of cryptic splice sites." Blood 100, no. 13 (December 15, 2002): 4478–84. http://dx.doi.org/10.1182/blood-2002-06-1647.
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Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aα, 6 in the γ, and only 2 in the Bβ fibrinogen–chain genes. Here, 2 afibrinogenemic probands, showing undetectable levels of functional fibrinogen, were screened for causative mutations at the genomic level. Sequence analysis of the 3 fibrinogen genes disclosed 2 novel homozygous mutations in introns 6 and 7 of the Bβ-chain gene (IVS6 + 13C > T and IVS7 + 1G > T), representing the first Bβ-chain gene splicing mutations described in afibrinogenemia. The IVS6 + 13C > T mutation predicts the creation of a donor splice site in intron 6, whereas the IVS7 + 1G > T mutation causes the disappearance of the invariant GT dinucleotide of intron 7 donor splice site. To analyze the effect of these mutations, expression plasmids containing Bβ-chain minigene constructs, either wild-type or mutant, were transfected in HeLa cells. Assessed by semiquantitative analysis of reverse transcriptase–polymerase chain reaction products, the IVS7 + 1G > T mutation resulted in multiple aberrant splicings, while the IVS6 + 13C > T mutation resulted in activation of a new splice site 11 nucleotides downstream of the physiologic one. Both mutations are predicted to determine protein truncations, supporting the importance of the C-terminal domain of the Bβ chain for fibrinogen assembly and secretion.
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Themistocleous, Christos, Anastasios Pagiaslis, Andrew Smith, and Christian Wagner. "A comparison of scale attributes between interval-valued and semantic differential scales." International Journal of Market Research 61, no. 4 (March 12, 2019): 394–407. http://dx.doi.org/10.1177/1470785319831227.
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This article presents the results of an exploratory study comparing interval-valued scales (IVSs) and semantic differential scales (SDSs). The article investigates consumer perceptions regarding specific scale attributes and utilizes a controlled, between-subjects, experimental pen-and-paper design to assess the preferences of respondents when using the IVSs and SDSs. The rationale of this comparison lies with the fact that the newly introduced IVS has a built-in mechanism that allows the direct capture of respondent uncertainty toward the asked question, a feature that is absent from the SDS and other widely used, single-point capturing scales in marketing research such as the Likert and Stapel. Results show that overall consumer preferences of the IVS and SDS are equal, although “speed of use” results favor the IVS. The consistency of respondent evaluations regarding the two scales may indicate their interchangeability in marketing research and opens up pathways for future exploration of IVSs for the accumulation of more reliable and robust results. The main contribution of the article is the introduction of a novel IVS, within the context of marketing, for collecting respondent answers while also directly capturing respondent uncertainty. Furthermore, this article adds to the discussion of consumer perceptions and preferences regarding different scales, scale development, and optimal rating scales that may lessen ambiguity for survey respondents and researchers.
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Blum, David A. "Factors Contributing To Independent Venture Capital Successful Exits." Journal of Business & Economics Research (JBER) 13, no. 1 (January 26, 2015): 1. http://dx.doi.org/10.19030/jber.v13i1.9074.
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Independent venture capital (IVC) firms invest in nascent, high growth, high risk, and market scalable companies for the purposes of achieving a successful exit. An exit is the primary method IVCs use to receive a return on investment. Although IVCs provide capital funding, strategic advice, and access to an extensive network of potential suppliers and customers, approximately 20% of portfolio firms reach a successful exit. This paper outlines the job of the IVC, the due diligence and staging processes, and addresses four factors that might account for the low successful exit rate: 1) diseconomy of scale in the venture capital industry, 2) emphasis on quick exits rather than building long-term sustainable companies, 3) exits that are independent of fund inflows, and 4) financial and market forecasts that appear to trump market conditions. This paper addresses a gap in literature by providing four factors contributing to low IVC success exit rates. To achieve higher exit successes, IVCs need to cease providing funding capital, especially during times of high capital inflows, and stop chasing portfolio firms that have little chance of achieving a successful exit.
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Anwer, Zaheer. "Islamic venture capital investment style – opportunities and challenges." Journal of Islamic Marketing 10, no. 3 (September 9, 2019): 848–59. http://dx.doi.org/10.1108/jima-02-2018-0046.
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Purpose This study aims to explore how Islamic venture capital (IVC) structure can be established by introducing modifications in traditional venture capital (VC) structure. The motivation stems from the criticism on the existing Islamic finance products, that are said to be Shariah-compliant in form but do not fulfil objectives of Shariah whereas IVC is portrayed by existing literature as an ideal risk sharing based product. Design/methodology/approach This study uses a questionnaire method to understand IVC philosophy, structure and operational approach and asked the respondents to identify how IVC differs in respect of these traits from conventional VC. The authors collected 50 questionnaires from IVC practitioners, regulators, academicians and Islamic finance (IF) consultants in three countries, namely, Malaysia, Pakistan and Turkey. Findings IVC can be incorporated by introducing some modifications in traditional VC structure. They need to appoint a full-time Shariah scholar, to ensure compliance to Shariah principles. IVCs should refrain from dealing in impermissible business activities. They can choose any prevailing method for valuation and investment mode, provided it follows principles of Shariah. IVCs are exposed to unique risks such as Shariah non-compliance risk and equity investment risk and they need additional measures to safeguard against these risks. They can adopt any exit strategy, provided funds are procured from halal sources. Finally, IVC is found to hold the potential to achieve the desired objectives of IF. Originality/value This study fills the gap in the existing literature related to IVC investments as no study, to the best of the author’s knowledge, has evaluated the dynamics of IVC by using responses from industry, academia and regulators.
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Ryu, Jeong Seon, Eun Soon Shin, Hyun-Jung Kim, Hae-Seong Nam, Jong-Eun Lee, and Joo Han Lim. "Lack of association of genetic variations of deoxycytidine kinase with toxicity or survival of non-small cell lung cancer patients treated with gemcitabine plus cisplatin." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13065-e13065. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13065.
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e13065 Background: To determine whether tagging polymorphisms (tSNPs) of deoxycytidine kinase (DCK) have an effect on toxicity or prognosis in patients with non–small-cell lung cancer (NSCLC) treated with gemcitabine plus cisplatin. Methods: Three tSNPs (−201 C>T, rs2306744; IVS2+9846 G>A, rs12648166; IVS6+1392 T>C, rs4694362) were chosen using two databases, the international HapMap Project and Japanese Single-Nucleotide Polymorphisms. Genotyping was performed using the Genome Lab SNPstream Genotyping System and SNaPShot assay kit. We evaluated the associations of the tSNPs with hematologic toxicity or overall survival of 139 NSCLC patients at stages IIIA/IIIB (59) and IV (80). Results: The median survival time of the patients was 11.9 months. Hematologic toxicity such as neutropenia, thrombocytopenia and anemia were not different by the three tSNPs or haplotypes (CGT, CAT and CAC) of DCK. The genetic variations did not affect on survival of the patients (log-rank P: 0.248 for −201 C>T, 0.571 for IVS2+9846 G>A, 0.686 for IVS6+1392 T>C, 0,556 for CGT, 0.453 for CAT and 0.845 for CAC). In Cox model, these tSNPs and haplotypes did not reveal prognostic relevance (aHR and 95%CI: 0.954 and 0.611 to 1.489 for −201 C>T; 1.193 and 0.719 to 1.979 for IVS2+9846 G>A; 1.072 and 0.674 to 1.706 for IVS6+1392 T>C, 0,668 and 0.205 to 2.175 for CGT, 1.043 and 0.713 to 1.525 for CAT and1.043 and 0.701 to 1.550 for CAC). Conclusions: This is the first study to focus on the association of tSNPs and their haplotypes of DCK with toxicity and survival in NSCLC patients. This suggests that genetic variations of DCK have no effect on the outcomes in the patients treated with gemcitabine-based chemotherapy.
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Ivanoshchuk, Dinara E., Elena V. Shakhtshneider, Oksana D. Rymar, Alla K. Ovsyannikova, Svetlana V. Mikhailova, Veniamin S. Fishman, Emil S. Valeev, Pavel S. Orlov, and Mikhail I. Voevoda. "The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients." Journal of Personalized Medicine 11, no. 1 (January 18, 2021): 57. http://dx.doi.org/10.3390/jpm11010057.
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Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A.
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Kumar, Sushil, Ritwik Baidya, and Prakash Baral. "Double inferior vena cava with multiple interconnections – a rare case report." Journal of Gandaki Medical College-Nepal 13, no. 2 (December 25, 2020): 192–94. http://dx.doi.org/10.3126/jgmcn.v13i2.30356.
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Duplication of the inferior vena cava (IVC) has been estimated to occur in 0.2% to 3% of the population. Although rare, the presence of double inferior vena cava is important to recognize as it has important implications. Diagnostic confusion in interpreting imaging results can arise when a venous anomaly is mistaken for a pathologic process like lymphadenopathy. If such patient were to need an IVC filter placement, separate filters would be required, one for the right and one for the left IVCs. A vascular surgeon would need to be aware of these anomalies to perform safe surgery of the retroperitoneal organs. We present a case of duplicated IVC, which was observed during routine dissection of a 58-year-old male cadaver. Left IVC was communicating with left renal vein superiorly. The left renal vein was running obliquely behind the abdominal aorta. Also, the left IVC was connected to right IVC by one transverse anastomosing vessel. The two-retroaortic communication between right and left IVC make this case report unique.
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Foglieni, Barbara, Laura Cremonesi, Maurizio Travi, Anna Ravani, Antonino Giambona, Maria Cristina Rosatelli, Chiara Perra, Paolo Fortina, and Maurizio Ferrari. "β-Thalassemia Microelectronic Chip: A Fast and Accurate Method for Mutation Detection." Clinical Chemistry 50, no. 1 (January 1, 2004): 73–79. http://dx.doi.org/10.1373/clinchem.2003.023077.
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Abstract Background: β-Thalassemia is one of the most common genetic diseases in humans. We developed an automated electronic microchip for fast and reliable detection of the nine most frequent mutations accounting for >95% of the β-thalassemia alleles in the Mediterranean area. Methods: We developed a microchip-based assay to identify the nine most frequent mutations (cd39C>T, IVS1-110G>A, IVS1-1G>A, IVS1-6T>C, IVS2-745C>G, cd6delA, −87C>G, IVS2-1G>A, and cd8delAA) by use of the Nanogen Workstation. The biotinylated amplicon was electronically addressed on the chip to selected pads, where it remained embedded through interaction with streptavidin in the permeation layer. The DNA at each test site was then hybridized to a mixture of fluorescently labeled wild-type or mutant probes. Results: Assays conditions were established based on the analysis of 700 DNA samples from compound heterozygotes or homozygotes for the nine mutations. The assays were blindly validated on 250 DNA samples previously genotyped by other methods, with complete concordance of results. Alternative multiplexed formats were explored: the combination of multiplex PCR with multiple addressing and/or hybridization allowed analysis of all nine mutations in the same sample on one test site of the chip. Conclusions: The open flexible platform can be designed by the user according to the local prevalence of mutations in each geographic area and can be rapidly extended to include the remaining mutations causing β-thalassemia in other regions of the world.
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Hecksel, Kathleen A., Gordon W. Dewald, and David P. Steensma. "Ferrochelatase Mutation Screening by Denaturing High Performance Liquid Chomatography in Idiopathic Acquired Sideroblastic Anemia (Refractory Anemia with Ringed Sideroblasts) and Erythrocytic Protoporphyria." Blood 106, no. 11 (November 16, 2005): 3735. http://dx.doi.org/10.1182/blood.v106.11.3735.3735.
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Abstract BACKGROUND: The molecular etiology of idiopathic acquired sideroblastic anemia (IASA), now considered a form of myelodysplastic syndrome, is currently unknown. Romslo et al (Blood 1982) reported a patient with IASA who had moderately elevated free erythrocytic protoporphyrin (FEP); this observation is now frequently made in IASA, helping distinguish IASA (high FEP) from inherited sideroblastosis (low FEP). In addition, rare patients with erythropoietic protoporphyria (EPP)—defined by cutaneous photosensitivity, dramatically elevated FEP levels, and germline point mutations in the ferrochelatase (FECH) gene at 18q21.3—have ringed sideroblasts in their marrow. We hypothesized that patients with IASA might have acquired somatic FECH mutations. METHODS AND RESULTS: We designed a denaturing high performance liquid chromatography (DHPLC) assay to explore this possibility and to avoid problems related to mutation screening in the setting of mixed clonality. To validate the DHPLC assay, the coding region of the FECH gene from 2 molecularly undiagnosed EPP patients without liver disease was analyzed. In one patient, both a heterozygous 69delG mutation (GenBank Accession NM_000140) and heterozygosity for the FECH expression-modulating IVS3-48C/T polymorphism were detected. In the other patient, no FECH coding mutations or polymorphisms were detected, either by DHPLC or conventional dye sequencing. FEP measurements were then obtained on 2 IASA patients and were elevated (65 and 115 mcg/dL; normal 1–10 mcg/dL) with normal urine and fecal porphyrins. Genomic DNA obtained from these 2 patients as well as archival DNA from 30 other patients with IASA was amplified and tested for FECH mutations. No coding region mutations were detected. Synonymous polymorphisms in exon 7 (rs536765) and 9 (rs536560) were found in 6/32 (19%; normal heterozygosity 0.398) and 14/32 (44%; normal heterozygosity 0.402) samples, respectively. The IVS3-48C/T polymorphism (rs2272783) was found in 3/32 (9%) (prevalence in the general population is 11%, Gouya Nat Genet 2002). In addition, 3 intronic polymorphisms not in the refSNP database were detected: IVS8+34 C/T (2/32), IVS8-61delG (5/32), and IVS9-59delA (2/32). CONCLUSION: IASA is not associated with coding mutations in FECH. Elevation of FEP in ASA must instead be due to the lack of mitochondrial iron in the proper form for incorporation into the porphyrin ring; attention should instead focus on factors responsible for maintaining the appropriate redox state and compartmentalization of iron. DHPLC can detect FECH mutations and polymorphisms, but because of the high frequency of the latter and the consequent need to sequence multiple exons, it is not a practical screening tool for studying undiagnosed EPP patients.
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Kubota, C., T. Kojima, T. Nagai, X. Tian, and X. Yang. "346 BOVINE EMBRYO DEVELOPMENT AFTER IVM/IVF/IVC OF OOCYTES STORED FOR 22 H IN VARIOUS MEDIA." Reproduction, Fertility and Development 19, no. 1 (2007): 288. http://dx.doi.org/10.1071/rdv19n1ab346.
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The timing of IVM–IVF–IVC is restricted by the onset of oocyte maturation, and sometimes oocytes must be treated at midnight. If we could regulate the timing of IVM of oocytes without decreasing their developmental competence, the IVM–IVF–IVC system could be a more applied technology. The present study was performed to examine the effects of in vitro storage of bovine oocytes in simple media prior to maturation culture to manipulate the start of IVM. Bovine follicular fluid (bFF), Dulbecco's PBS (PBS), M199 Earle salts (M199), and Earle salts supplemented with 5 mM NaHCO3 (M199A) were used as the fundamental media, after an addition of antibiotics, for in vitro storage of bovine cumulus–oocyte complexes (COCs) collected from ovaries obtained at the slaughterhouse. The fundamental media except for bFF were supplemented with 10% fetal bovine serum (FBS) or 1 mg mL−1 polyvinyl alcohol (PVA). COCs were collected from follicles (3–8 mm in diameter) and washed twice in each medium; then approximately 50 COCs were submerged in 1 mL of each medium in cryotubes (Falcon #2812, 2.5 mL; Becton Dickinson Labware, Lincoln, NJ, USA), which were stored in a container kept at 38.5°C for 22 h under air-closed condition (in vitro storage: IVS). Subsequently, the stored COCs were in vitro-matured (IVM) for 22 h in M199 with 10% FBS and 20 µg mL−1 estradiol, fertilized (IVF), and cultured in CR1aa (IVC) for examination of their development to the blastocyst stage (Kubota et al. 1998 Mol. Reprod. Dev. 51, 281–286). Fresh oocytes without IVS were used as controls. The nuclear status of oocytes after IVS–IVM was compared to that of control oocytes by aceto-orcein stain. Their developmental rates to the blastocyst stage after IVM–IVF–IVC were compared between experimental and control groups. The experiment was repeated more than 3 times, and results were statistically analyzed using Student's t-test. When bFF and PBS supplemented with FBS or PVA were used for IVS, the rates of survived COCs after IVS and the development to the blastocyst stage after IVM–IVF–IVC (bFF (n = 87): 0%, 0%; PBS/FBS (n = 72): 84%, 1%; and PBS/PVA (n = 81): 89%, 6%, respectively) were significantly lower than those of the control group (n = 406; 97% and 29%, respectively). On the other hand, when M199A supplemented with FBS or PVA was used for IVS, the survival rate after IVS and the developmental rate to the blastocyst stage after IVS–IVM–IVF (M199A/FBS (n = 97): 82%, 28%; and M199A/PVA (n = 111): 98%, 31%, respectively) did not differ from those of the control group. After IVS, cumulus expansion was not seen and most of the oocyte nuclei reached the GVBD stage. These results suggest that the nuclear maturation progress of bovine oocytes can be regulated for at least 22 h in M199A without any deleterious influence on the number of oocytes surviving at an immature state after the storage and their subsequent development to the blastocyst stage after IVM–IVF–IVC. The delayed maturation allows a flexible fertilization schedule which is advantageous in research and industrial applications.
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Buchman, A. R., and P. Berg. "Comparison of intron-dependent and intron-independent gene expression." Molecular and Cellular Biology 8, no. 10 (October 1988): 4395–405. http://dx.doi.org/10.1128/mcb.8.10.4395.
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Recombinant simian virus 40 viruses carrying rabbit beta-globin cDNA failed to express the beta-globin sequence unless an intron was included in the transcription unit. The addition of either beta-globin IVS1 or IVS2 caused a 400-fold increase in RNA production. Stable beta-globin RNA production required sequences in IVS2 that were very close to the splice sites and that coincided with those needed for mRNA splicing. In addition to the recombinant viruses, intron-dependent expression was observed with both replicating and nonreplicating plasmid vectors in short-term transfections of cultured animal cells. Unlike transcriptional enhancer elements, IVS2 failed to increase stable RNA production when it was placed downstream of the polyadenylation site. Using a plasmid vector system to survey different inserted sequences for their dependence on introns for expression, we found that the presence of IVS2 stimulated the expression of these sequences 2- to 500-fold. Sequences from the transcribed region of the herpes simplex virus thymidine kinase gene, a gene that lacks an intervening sequence, permitted substantial intron-independent expression (greater than 100-fold increase) in the plasmid vector system.
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Buchman, A. R., and P. Berg. "Comparison of intron-dependent and intron-independent gene expression." Molecular and Cellular Biology 8, no. 10 (October 1988): 4395–405. http://dx.doi.org/10.1128/mcb.8.10.4395-4405.1988.
Full textAbstract:
Recombinant simian virus 40 viruses carrying rabbit beta-globin cDNA failed to express the beta-globin sequence unless an intron was included in the transcription unit. The addition of either beta-globin IVS1 or IVS2 caused a 400-fold increase in RNA production. Stable beta-globin RNA production required sequences in IVS2 that were very close to the splice sites and that coincided with those needed for mRNA splicing. In addition to the recombinant viruses, intron-dependent expression was observed with both replicating and nonreplicating plasmid vectors in short-term transfections of cultured animal cells. Unlike transcriptional enhancer elements, IVS2 failed to increase stable RNA production when it was placed downstream of the polyadenylation site. Using a plasmid vector system to survey different inserted sequences for their dependence on introns for expression, we found that the presence of IVS2 stimulated the expression of these sequences 2- to 500-fold. Sequences from the transcribed region of the herpes simplex virus thymidine kinase gene, a gene that lacks an intervening sequence, permitted substantial intron-independent expression (greater than 100-fold increase) in the plasmid vector system.
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Kivelev, Juri, Mika Niemelä, Riku Kivisaari, and Juha Hernesniemi. "Intraventricular cerebral cavernomas: a series of 12 patients and review of the literature." Journal of Neurosurgery 112, no. 1 (January 2010): 140–49. http://dx.doi.org/10.3171/2009.3.jns081693.
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Object Intraventricular cavernomas (IVCs) occur in only 2–10% of patients with cerebral cavernomas. Reports concerning IVC are scarce and are limited mostly to sporadic case reports. In this paper, the authors present a series of 12 patients with IVCs that were treated at a single neurosurgical department. In addition, the authors reviewed the literature. Methods All clinical data were analyzed retrospectively. Follow-up questionnaires were sent to all patients. Outcome was assessed using the Glasgow Outcome Scale. The authors also conducted a PubMed search and found 77 cases of IVC. Results The patients' median age was 47 years, and the male/female ratio was 2:1. A cavernoma occurred in the lateral ventricle in 6 patients, in another 5 it was in the fourth ventricle, and 1 had a lesion in the third ventricle. Almost all patients presented with acute headache on admission and in more than half, the symptoms were related to cavernoma bleeding. In total, 8 rebleedings occurred in 5 patients during a median of 0.4 years. Three patients with a cavernoma of the fourth ventricle presented with a cranial nerve deficit. In 8 cases, a cavernoma was surgically treated an average of 1.3 years after the diagnosis. Only 1 patient underwent surgery in the acute phase after a major intraventricular/intracerebral hemorrhage. The median follow-up time was 2 years. No patient was lost to follow-up, and no patient died. In total, on follow-up 9 patients improved and 3 had a persistent neurological deficit, of which 2 existed before surgery. Conclusions In the present series, the IVCs had a high tendency for rehemorrhage. Surgery is advocated when hemorrhages are frequent, and the mass effect causes progressive neurological deficits. Microsurgical removal of the IVC is safe, but in the fourth ventricle it can carry increased risk for cranial nerve deficits.
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Pabbaraju, Kanti, Wayne L. Miller, and Kenneth E. Sanderson. "Distribution of Intervening Sequences in the Genes for 23S rRNA and rRNA Fragmentation among Strains of theSalmonella Reference Collection B (SARB) and SARC Sets." Journal of Bacteriology 182, no. 7 (April 1, 2000): 1923–29. http://dx.doi.org/10.1128/jb.182.7.1923-1929.2000.
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ABSTRACT Intervening sequences (IVSs) occur sporadically in several bacterial genera in the genes for 23S rRNA at relatively conserved locations. They are cleaved after transcription and lead to the presence of fragmented rRNA, which is incorporated into the ribosomes without religation but is nevertheless functional. The fragmentation of rRNA and the number of IVSs in all 72 strains of theSalmonella Reference Collection B set and 16 strains of theSalmonella Reference Collection C set, which have been established on the basis of multilocus enzyme electrophoresis (MLEE), were analyzed in the present study. Fragmentation of 23S rRNA was restricted to conserved cleavage sites located at bp 550 (helix 25) and bp 1170 (helix 45), locations where IVSs have been reported. Random cleavage at sites where IVSs could not be detected was not seen. Uncleaved IVSs were not detected in any case; thus, the IVSs invariably led to rRNA fragmentation, indicating a strong selection for maintenance of RNase III cleavage sites. The distribution of the number of IVSs carried by the different strains in the seven rrlgenes is diverse, and the pattern of IVS possession could not be related to the MLEE pattern among the various Salmonellastrains tested; this indicates that the IVSs are frequently exchanged between strains by lateral transfer. All eight subspecies of the genus Salmonella, including subspecies V represented bySalmonella bongori, have IVSs in both helix 25 and helix 45; this indicates that IVSs entered the genus after its divergence from Escherichia coli (more than 100 million years ago) but before separation of the genus Salmonella into many forms or that they were in the ancestor but have been lost fromEscherichia.
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Evguenieva-Hackenberg, Elena, and Gabriele Klug. "RNase III Processing of Intervening Sequences Found in Helix 9 of 23S rRNA in the Alpha Subclass of Proteobacteria." Journal of Bacteriology 182, no. 17 (September 1, 2000): 4719–29. http://dx.doi.org/10.1128/jb.182.17.4719-4729.2000.
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ABSTRACT We provide experimental evidence for RNase III-dependent processing in helix 9 of the 23S rRNA as a general feature of many species in the alpha subclass of Proteobacteria(alpha-Proteobacteria). We investigated 12Rhodobacter, Rhizobium,Sinorhizobium, Rhodopseudomonas, andBartonella strains. The processed region is characterized by the presence of intervening sequences (IVSs). The 23S rDNA sequences between positions 109 and 205 (Escherichia coli numbering) were determined, and potential secondary structures are proposed. Comparison of the IVSs indicates very different evolutionary rates in some phylogenetic branches, lateral genetic transfer, and evolution by insertion and/or deletion. We show that the IVS processing inRhodobacter capsulatus in vivo is RNase III-dependent and that RNase III cleaves additional sites in vitro. While all IVS-containing transcripts tested are processed in vitro by RNase III from R. capsulatus, E. coli RNase III recognizes only some of them as substrates and in these substrates frequently cleaves at different scissile bonds. These results demonstrate the different substrate specificities of the two enzymes. Although RNase III plays an important role in the rRNA, mRNA, and bacteriophage RNA maturation, its substrate specificity is still not well understood. Comparison of the IVSs of helix 9 does not hint at sequence motives involved in recognition but reveals that the “antideterminant” model, which represents the most recent attempt to explain the E. coli RNase III specificity in vitro, cannot be applied to substrates derived from alpha-Proteobacteria.
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Qian, L., L. Theodor, M. Carter, M. N. Vu, A. W. Sasaki, and M. F. Wilkinson. "T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates." Molecular and Cellular Biology 13, no. 3 (March 1993): 1686–96. http://dx.doi.org/10.1128/mcb.13.3.1686.
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The expression of functional T cell receptor-beta (TCR-beta) transcripts requires the activation of programmed DNA rearrangement events. It is not clear whether other mechanisms dictate TCR-beta mRNA levels during thymic ontogeny. We examined the potential role of RNA splicing as a regulatory mechanism. As a model system, we used an immature T cell clone, SL12.4, that transcribes a fully rearranged TCR-beta gene but essentially lacks mature 1.3-kb TCR-beta transcripts in the cytoplasm. Abundant TCR-beta splicing intermediates accumulate in the nucleus of this cell clone. These splicing intermediates result from inefficient or inhibited excision of four of the five TCR-beta introns; the only intron that is efficiently spliced is the most 5' intron, IVSL. The focal point for the regulation appears to be IVS1C beta 1 and IVS2C beta 1, since unusual splicing intermediates that have cleaved the 5' splice site but not the 3' splice site of these two introns accumulate in vivo. The block in 3' splice site cleavage is of interest since sequence analysis reveals that these two introns possess canonical splice sites. A repressional mechanism involving a labile repressor protein may be responsible for the inhibition of RNA splicing since treatment of SL12.4 cells with the protein synthesis inhibitor cycloheximide reversibly induces a rapid and dramatic accumulation of fully spliced TCR-beta transcripts in the cytoplasm, concomitant with a decline in TCR-beta pre-mRNAs in the nucleus. This inducible system may be useful for future studies analyzing the underlying molecular mechanisms that regulate RNA splicing.
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Qian, L., L. Theodor, M. Carter, M. N. Vu, A. W. Sasaki, and M. F. Wilkinson. "T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates." Molecular and Cellular Biology 13, no. 3 (March 1993): 1686–96. http://dx.doi.org/10.1128/mcb.13.3.1686-1696.1993.
Full textAbstract:
The expression of functional T cell receptor-beta (TCR-beta) transcripts requires the activation of programmed DNA rearrangement events. It is not clear whether other mechanisms dictate TCR-beta mRNA levels during thymic ontogeny. We examined the potential role of RNA splicing as a regulatory mechanism. As a model system, we used an immature T cell clone, SL12.4, that transcribes a fully rearranged TCR-beta gene but essentially lacks mature 1.3-kb TCR-beta transcripts in the cytoplasm. Abundant TCR-beta splicing intermediates accumulate in the nucleus of this cell clone. These splicing intermediates result from inefficient or inhibited excision of four of the five TCR-beta introns; the only intron that is efficiently spliced is the most 5' intron, IVSL. The focal point for the regulation appears to be IVS1C beta 1 and IVS2C beta 1, since unusual splicing intermediates that have cleaved the 5' splice site but not the 3' splice site of these two introns accumulate in vivo. The block in 3' splice site cleavage is of interest since sequence analysis reveals that these two introns possess canonical splice sites. A repressional mechanism involving a labile repressor protein may be responsible for the inhibition of RNA splicing since treatment of SL12.4 cells with the protein synthesis inhibitor cycloheximide reversibly induces a rapid and dramatic accumulation of fully spliced TCR-beta transcripts in the cytoplasm, concomitant with a decline in TCR-beta pre-mRNAs in the nucleus. This inducible system may be useful for future studies analyzing the underlying molecular mechanisms that regulate RNA splicing.
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Vörös, Károly, Csaba Hetyey, Jenő Reiczigel, and Gábor Czirok. "M-mode and two-dimensional echocardiographic reference values for three Hungarian dog breeds: Hungarian Vizsla, Mudi and Hungarian Greyhound." Acta Veterinaria Hungarica 57, no. 2 (June 1, 2009): 217–27. http://dx.doi.org/10.1556/avet.57.2009.2.3.
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The aim of the study was to establish normal reference echocardiographic values for three Hungarian dog breeds, and to determine the potential dependence of intracardiac parameters on body weight, age and gender. M-mode and two-dimensional echocardiography were performed on 95 clinically healthy dogs including 45 Hungarian Vizslas, 28 Mudis and 22 Hungarian Greyhounds. Linear intracardiac measurements included interventricular septal thickness (IVS), left ventricular internal diameter (LVID), left ventricular posterior wall thickness (LVPW) both in systole and diastole, as well as left atrial internal diameter (LAD), and aortic diameter (AOD) in early diastole. Fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes (EDV and ESV), as well as LAD:AOD ratio were calculated from the linear parameters. Mean, range and standard deviation of measurements were calculated for each breed. Body weight positively correlated in all three breeds with all left ventricular dimensions, such as IVSd, IVSs, LVIDd, LVIDDs, LVPWdand LVPWsparameters. LA values showed positive correlations to body weight in all three breeds. AOD and LA demonstrated a positive correlation with body weight in Hungarian Vizslas and Mudis, whilst the LAD:AOD ratio was related to body weight only in Mudis. Gender did not correlate with any of the measured echocardiographic parameters in any breeds. In Mudis, a positive correlation was found between the LAD:AOD ratio and age, as well as between the LAD:AOD ratio and E point to septal separation (EPSS).