Identification of hydrophobic sites on UV irradiated beta crystallins from bovine lenses [abstract]

Abstract only availableFaculty Mentor: Dr. Krishna Sharma, OphthalmologyThe lens of the eye is an avascular tissue of a complex network of proteins surrounded by a capsule. The three major protein families: alpha, beta, and gamma crystallins account for 95% of the lens proteins. These crystallins over time may change from their postranslational structure due to environmental factors and aging. During aging and cataractogenesis, lens proteins show increased aggregation. To determine the role of hydrophobic sites in lens protein aggregation we performed a beta crystallin aggregation assay and investigated whether there is increased exposure of hydrophobic sites prior to aggregation. Lens proteins were fractionated in a Sephadex G-200 column and the beta crystallin peak was collected. Beta crystallins in 50mM phosphate buffer (pH 7.4) were irradiated for 3 hours at 295 nm. Prior to irradiation and at every half hour interval the 360nm scattering was recorded and an aliquot of the sample was mixed with bis-ANS for the fluorescence to be measured (Ex390/Em490). Both, fluorescence and light scattering increased in parallel during the experiment. However, bis-ANS interaction studies have shown that there is an increased exposure of hydrophobic, bis-ANS binding sites in beta crystallins exposed to UV light, prior to the formation of light scattering protein aggregates. This suggests to us that initial exposure of hydrophobic sites in beta crystallins is necessary for the protein aggregation. Similar results were obtained when the beta crystallins were denatured by chemical method involving Cu 2+ ions and H2O2. Studies are underway to identify the newly exposed hydrophobic sites in UV-treated beta crystallins

Pemanfaatan Aplikasi Kelas Kita Untuk Meningkatkan Motivasi Belajar Kimia Siswa SMA Pusaka 1 Jakarta T.A 2018/2019

Penelitian ini bertujuan untuk: (1) mengetahui apakah terdapat peningkatan motivasi belajar kimia siswa melalui pemanfaatan aplikaksi KelasKita, (2) mengetahui berapa besar peningkatan motivasi belajar kimia siswa melalui pemanfaatan aplikasi KelasKita. Desain penelitian ini menggunakan nonequivalent control group desain. Populasi penelitian adalah seluruh siswa kelas XI di SMA Pusaka 1 Jakarta semester II Tahun Ajaran 2018/2019. Sampel penelitian terdiri dari dua kelas dengan jumlah sampel 44 siswa yang ditentukan dengan purposive sampling, yaitu kelas XI IPA 3 sebagai kelas eksperimen dengan jumlah siswa 22 orang yang diberi perlakuan dengan menggunakan model pembelajaran inkuiri terbimbing dengan memanfaatkan aplikasi KelasKita dan kelas XI IPA 1 sebagai kelas kontrol dengan jumlah siswa 22 siswa yang menggunakan model pembelajaran inkuiri terbimbing tanpa memanfaatkan aplikasi apapun. Instrumen penelitian berupa angket dengan jumlah 13 butir pernyataan, dengan skala pengukuran menggunakan skala likert jumlah pilihan jawaban sebanyak 4 pilihan dari tidak pernah sampai sangat setuju. Uji persyaratan analisis dengan menggunakan data pre nontest menunjukkan bahwa data terdistribusi normal dan bersifat homogen. Uji hipotesis yang dilakukan dengan uji parametrik yaitu uji paired sample t test pada taraf signifikan 0.05 dengan bantuan SPSS for Windows Versi 22.0. Hasil penelitian ini memperoleh thitung (5.778) > ttabel (2.416) dan sig. 0.00 < 0.05. Berdasarkan analisis data dan uji hipotesis yang dilakukan diperoleh bahwa terdapat peningkatan motivasi belajar kimia siswa melalui pemanfaatan aplikasi KelasKita. Berapa besar peningkatan motivasi belajar kimia siswa melalui pemanfaatan aplikasi KelasKita dengan menggunakan uji gain diperoleh hasil sebesar 0.478 pada kategori sedang. Kata kunci : aplikasi, kelaskita, kimia koloid, media, motivasi belajar. This research aims to: (1) determine whether there is an increase in students’ motivation to learn chemistry through the utilization of the KelasKita application, (2) know how much chemistry learning motivation improve by use KelasKita Application. The design of this research uses nonequivalent control group design. The study population was all students of class XI at Pusaka 1 Jakarta High School in the second semester of the Academic Year 2018/2019. The study sample consisted of two classes with a sample of 44 students determined by purposive sampling, while class 11 Science 3 as an experimental class with 22 students treated by using a guided inquiry learning model with KelasKita applications and class 11 Science 1 as a class control with 22 students who use a guided inquiry learning model without utilizing any application. The research instrument was in the form of a questionnaire with a number of 13 items of statements, with the scale of measurement using the likert scale the number of answer choices as many as 4 choices from never to very agree. Test requirements analysis using pre nontest data shows that data is normally distributed and homogeneous. Hypothesis testing conducted by parametric test is a paired sample t test at a significant of 0.05 with the help of SPSS for Windows Version 22.0. The results of this research obtained tcount (5.778) > ttable (2.416) and sig. 0.00 < 0.05. Based on data analysis and hypothesis testing conducted, it was found that there was an increase in students’ chemistry learning motivation through the use of KelasKita applications. How much is the increase in students’ chemistry learning motivation through the utilization of the KelasKita application by using the gain test obtained 0.478 results in the medium category. Keyword : application, colloid chemistry, kelasita, media, motivation to learn

Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America. Specifically, for syndromes with increased risk for WT, we recommend renal ultrasounds every 3 months from birth (or the time of diagnosis) through the seventh birthday. For HB, we recommend screening with full abdominal ultrasound and alpha-fetoprotein serum measurements every 3 months from birth (or the time of diagnosis) through the fourth birthday. We recommend that when possible, these patients be evaluated and monitored by cancer predisposition specialists. At this time, these recommendations are not based on the differential risk between different genetic or epigenetic causes for each syndrome, which some European centers have implemented. This differentiated approach largely represents distinct practice environments between the United States and Europe, and these guidelines are designed to be a broad framework within which physicians and families can work together to implement specific screening. Further study is expected to lead to modifications of these recommendations.This study was supported by NCI K08 CA1939915, Alex's Lemonade Stand Foundation for Childhood Cancer, and St. Baldrick's Foundation (to J.M. Kalish); European Research Council Advanced Researcher Award (to E.R. Maher); and NCI 5P30CA054174-21 (to G.E. Tomlinson)

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis.

Importance Guidelines for clinical management in Li-Fraumeni syndrome, a multiple-organ cancer predisposition condition, are limited. Whole-body magnetic resonance imaging (WBMRI) may play a role in surveillance of this high-risk population.Objective To assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline.Data sources Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium.Study selection Cohorts that incorporated WBMRI for individuals with germline TP53 mutations from January 1, 2004, through October 1, 2016, were included.Data extraction and synthesis Data were extracted by investigators from each cohort independently and synthesized by 2 investigators. Random-effects meta-analysis methods were used to estimate proportions.Main outcomes and measures The proportions of participants at baseline in whom a lesion was detected that required follow-up and in whom a new primary malignant neoplasm was detected.Results A total of 578 participants (376 female [65.1%] and 202 male [34.9%]; mean [SD] age, 33.2 [17.1] years) from 13 cohorts in 6 countries were included in the analysis. Two hundred twenty-five lesions requiring clinical follow-up were detected by WBMRI in 173 participants. Sixty-one lesions were diagnosed in 54 individuals as benign or malignant neoplasms. Overall, 42 cancers were identified in 39 individuals, with 35 new localized cancers treated with curative intent. The overall estimated detection rate for new, localized primary cancers was 7% (95% CI, 5%-9%).Conclusions and relevance These data suggest clinical utility of baseline WBMRI in TP53 germline mutation carriers and may form an integral part of baseline clinical risk management in this high-risk population

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

Genetic variation in apoptosis gene predicts neurocognitive impairment in children with medulloblastoma

Purpose: Medulloblastoma is the most common malignant brain tumor in children. As survival rates have risen, the importance of permanent side effects of therapy has grown. Neurocognitive impairment is one of the most prominent chronic toxicities of treatment. Age and craniospinal radiation (CSI) dose are established risk factors, however this adverse outcome cannot be predicted. We hypothesized that host genetic polymorphisms in pathways involved in the inflammatory response to radiation would be associated with neurocognitive impairment in children with medulloblastoma. ^ Experimental Design: This study included 40 children with medulloblastoma/primitive neuroectodermal tumor (PNET) seen at Texas Children\u27s Cancer Center or MD Anderson Cancer Center, who had been treated with CSI and had received a neuropsychological evaluation at least 9 months post-CSI. Subjects who had an intelligence-quotient score (full-scale, verbal, or performance) at or below 77.5 were deemed impaired. Genotyping of single nucleotide polymorphisms (SNPs) was performed using an Illumina HumanOmni1-Quad BeadChip. Only SNPs in relevant inflammation pathways were assessed. Odds ratios were estimated using unconditional logistic regression with adjustments for age group, CSI dose group, and a measure of population stratification. ^ Results: There were 19 children with neurocognitive impairment and 21 were unimpaired. In univariate analyses, these groups did not differ by demographic, disease, or therapy characteristics. No individual SNPs were associated with neurocognitive impairment in children with medulloblastoma/PNET. However, an apoptosis gene, Caspase-2 and Receptor Interacting Protein Kinase-1 Domain Containing Adaptor with Death Domain (CRADD ), haplotype (rs11107146, rs2304439, and rs12582133) was associated with the outcome in univariate and multivariable models. Subjects with an AGA haplotype were more than 7 times more likely to be impaired than those with a GAG haplotype (OR 7.8, 95%CI 1.1-53.9). ^ Conclusions: We have discovered a new association between CRADD and neurocognitive impairment in medulloblastoma/PNET. In the future, medulloblastoma patients with the at-risk genotypes may be considered for enrollment on clinical trials using reduced craniospinal radiation doses and/or novel anti-apoptotic strategies.