117 research outputs found
LKS Asam Basa Berbasis Pendekatan Ilmiah Dalam Meningkatkan KPS Berdasarkan Kognitif Siswa
This research aimed to describe the effectiveness of scientific approach based student worksheets in improving science process skills (SPS) insight from student\u27s cognitive. The method of this research was quasi experimental with 2x2 factorial design. The population of this research was all students of XI IPA SMAN 15 Bandarlampung on 2016/2017. The sample were XI IPA-4 and the XI IPA 2 which taken by purposive sampling. The data of this study were analyzed by using two ways ANOVA test and t test. The result of this research was no interaction between learning with scientific approach based worksheets and cognitive on SPS; learning process using student worksheets scientific approach was effective to improve SPS; SPS high and low cognitive ability with learning using worksheets Scientific Approach wass higher than conventional worksheets; SPS high cognitive ability was higher than low cognitive ability with learning using worksheets scientific approach. Penelitian ini bertujuan mendeskripsikan efektivitas LKS pendekatan ilmiah dalam meningkatkan KPS berdasarkan kognitif siswa. Metode penelitian menggunakan kuasi eksperimen dengan desain faktorial 2x2. Populasi penelitian seluruh siswa kelas XI IPA di SMAN 15 Bandarlampung tahun 2016/2017. Sampel penelitian ini kelas XI IPA 4 dan kelas XI IPA 2 yang diambil dengan teknik purposive sampling. Data penelitian dianalisis menggunakan uji two ways ANOVA dan uji t. Hasil penelitian menunjukan tidak terdapat interaksi antara pembelajaran menggunakan LKS terhadap KPS berdasarkan kemampuan kognitif, pembelajaran menggunakan LKS pendekatan ilmiah efektif untuk meningkatkan KPS, KPS siswa kognitif tinggi dan rendah dengan pembelajaran menggunakan LKS pendekatan ilmiah lebih tinggi dibandingkan LKS konvensional, KPS siswa kognitif tinggi lebih tinggi dibandingkan KPS siswa kognitif rendah menggunakan LKS pendekatan ilmiah
ProteoModlR for functional proteomic analysis
BACKGROUND: High-accuracy mass spectrometry enables near comprehensive quantification of the components of the cellular proteomes, increasingly including their chemically modified variants. Likewise, large-scale libraries of quantified synthetic peptides are becoming available, enabling absolute quantification of chemically modified proteoforms, and therefore systems-level analyses of changes of their absolute abundance and stoichiometry. Existing computational methods provide advanced tools for mass spectral analysis and statistical inference, but lack integrated functions for quantitative analysis of post-translationally modified proteins and their modification stoichiometry. RESULTS: Here, we develop ProteoModlR, a program for quantitative analysis of abundance and stoichiometry of post-translational chemical modifications across temporal and steady-state biological states. While ProteoModlR is intended for the analysis of experiments using isotopically labeled reference peptides for absolute quantitation, it also supports the analysis of labeled and label-free data, acquired in both data-dependent and data-independent modes for relative quantitation. Moreover, ProteoModlR enables functional analysis of sparsely sampled quantitative mass spectrometry experiments by inferring the missing values from the available measurements, without imputation. The implemented architecture includes parsing and normalization functions to control for common sources of technical variation. Finally, ProteoModlR’s modular design and interchangeable format are optimally suited for integration with existing computational proteomics tools, thereby facilitating comprehensive quantitative analysis of cellular signaling. CONCLUSIONS: ProteoModlR and its documentation are available for download at http://github.com/kentsisresearchgroup/ProteoModlR as a stand-alone R package. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1563-6) contains supplementary material, which is available to authorized users
Genomic instability promoted by expression of human transposase-derived gene
DNA Transposases are enzymes that recognize and catalyze the movement of mobile elements in the human genome known as transposons. There are abundant transposase-derived genes in the human genome that have been conserved through evolution. Some of them, such as PGBD5, maintain their enzymatic activity in human cells. The expression of PGBD5 has been related to mobilization of DNA transposons through a motif specific cut and paste mechanism across the genome. The excision and insertion mechanism of transposable elements can cause genomic rearrangements and have a potential mutagenic activity in specific disease cases such as cancer. In this study, we analyze how the expression of PGBD5 leads to genomic instabilit
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Colorimetric and Longitudinal Analysis of Leukocoria in Recreational Photographs of Children with Retinoblastoma
Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., “white eye”) in recreational photographs. A quantitative definition or scale of leukocoria – as it appears during recreational photography – has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent) remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop®) and standard color space conversion algorithms (operable in Microsoft Excel®) to quantify leukocoria in actual “baby pictures” of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings). One particular patient with bilateral retinoblastoma (“Patient Zero”) was photographed >7, 000 times by his parents (who are authors of this study) over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patient's life. This study establishes: (i) that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii) that Hue, Saturation and Value (i.e., HSV color space) are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii) that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv) the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography
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Antileukemic Activity of Nuclear Export Inhibitors that Spare Normal Hematopoietic Cells
Drugs that target the chief mediator of nuclear export, chromosome region maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic effects. Here, we report the structural analysis and antileukemic activity of a new generation of small-molecule inhibitors of CRM1. Designated selective inhibitors of nuclear export (SINE), these compounds were developed using molecular modeling to screen a small virtual library of compounds against the nuclear export signal (NES) groove of CRM1. The 2.2-Ă… crystal structure of the CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class of inhibitors, shows that the drug occupies part of the groove in CRM1 that is usually occupied by the NES, but penetrates much deeper into the groove and blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human acute myeloid leukemia (AML) cell lines representing different molecular subtypes of the disease. When administered orally to immunodeficient mice engrafted with human AML cells, KPT-251 had potent antileukemic activity with negligible toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent a novel class of drugs that warrant further testing in AML patients
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Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease
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Genomic DNA transposition induced by human PGBD5
Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. In this study, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vertebrates, can induce stereotypical cut-and-paste DNA transposition in human cells. Genomic integration activity of PGBD5 requires distinct aspartic acid residues in its transposase domain, and specific DNA sequences containing inverted terminal repeats with similarity to piggyBac transposons. DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. The apparent conservation of DNA transposition activity by PGBD5 suggests that genomic remodeling contributes to its biological function. DOI: http://dx.doi.org/10.7554/eLife.10565.00
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