bluuebunny/crossref_metadata_2025_split huggingface dataset:
asymptoticMK: A Web-Based Tool for the Asymptotic McDonald–Kreitman Test
Authors: Haller Benjamin C , Messer Philipp W 
Published: March 2017

Abstract
The McDonald–Kreitman (MK) test is a widely used method for quantifying the role of positive selection in molecular evolution. One key shortcoming of this test lies in its sensitivity to the presence of slightly deleterious mutations, which can severely bias its estimates. An asymptotic version of the MK test was recently introduced that addresses this problem by evaluating polymorphism levels for different mutation frequencies separately, and then extrapolating a function fitted to that data. Here, we present asymptoticMK, a web-based implementation of this asymptotic MK test. Our web service provides a simple R-based interface into which the user can upload the required data (polymorphism and divergence data for the genomic test region and a neutrally evolving reference region). The web service then analyzes the data and provides plots of the test results. This service is free to use, open-source, and available at http://benhaller.com/messerlab/asymptoticMK.html. We provide results from simulations to illustrate the performance and robustness of the asymptoticMK test under a wide range of model parameters.
From Pine Cones to Read Clouds: Rescaffolding the Megagenome of Sugar Pine (Pinus lambertiana)
Authors: Crepeau Marc W , Langley Charles H , Stevens Kristian A 
Published: March 2017

Abstract
We investigate the utility and scalability of new read cloud technologies to improve the draft genome assemblies of the colossal, and largely repetitive, genomes of conifers. Synthetic long read technologies have existed in various forms as a means of reducing complexity and resolving repeats since the outset of genome assembly. Recently, technologies that combine subhaploid pools of high molecular weight DNA with barcoding on a massive scale have brought new efficiencies to sample preparation and data generation. When combined with inexpensive light shotgun sequencing, the resulting data can be used to scaffold large genomes. The protocol is efficient enough to consider routinely for even the largest genomes. Conifers represent the largest reference genome projects executed to date. The largest of these is that of the conifer Pinus lambertiana (sugar pine), with a genome size of 31 billion bp. In this paper, we report on the molecular and computational protocols for scaffolding the P. lambertiana genome using the library technology from 10× Genomics. At 247,000 bp, the NG50 of the existing reference sequence is the highest scaffold contiguity among the currently published conifer assemblies; this new assembly’s NG50 is 1.94 million bp, an eightfold increase.
Schizosaccharomyces pombeMutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats
Authors: Villahermosa Desirée , Christensen Olaf , Knapp Karen , Fleck Oliver 
Published: March 2017

AbstractDefective mismatch repair (MMR) in humans is associated with colon cancer and instability of microsatellites, that is, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSα (Msh2-Msh6), which recognizes base-base mismatches and unpaired nucleotides in DNA, and MutLα (Mlh1-Pms1), which facilitates downstream steps. In addition, MutSβ (Msh2-Msh3) recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR. To test microsatellite stability in S. pombe and hence DNA loop repair, we have inserted tetra-, penta-, and hepta-nucleotide repeats in the ade6 gene and determined their Ade+ reversion rates and spectra in wild type and various mutants. Our data indicate that loops with four unpaired nucleotides in the nascent and the template strand are the upper limit of MutSα- and MutLα-mediated MMR in S. pombe. Stability of hepta-nucleotide repeats requires Msh3 and Exo1 in MMR-independent processes as well as the DNA repair proteins Rad50, Rad51, and Rad2FEN1. Most strikingly, mutation rates in the double mutants msh3 exo1 and msh3 rad51 were decreased when compared to respective single mutants, indicating that Msh3 prevents error prone processes carried out by Exo1 and Rad51. We conclude that Msh3 has no obvious function in MMR in S. pombe, but contributes to DNA repeat stability in MMR-independent processes.
Accuracy of Demographic Inferences from the Site Frequency Spectrum: The Case of the Yoruba Population
Authors: Lapierre Marguerite , Lambert Amaury , Achaz Guillaume 
Published: March 2017

AbstractSome methods for demographic inference based on the observed genetic diversity of current populations rely on the use of summary statistics such as the Site Frequency Spectrum (SFS). Demographic models can be either model-constrained with numerous parameters, such as growth rates, timing of demographic events, and migration rates, or model-flexible, with an unbounded collection of piecewise constant sizes. It is still debated whether demographic histories can be accurately inferred based on the SFS. Here, we illustrate this theoretical issue on an example of demographic inference for an African population. The SFS of the Yoruba population (data from the 1000 Genomes Project) is fit to a simple model of population growth described with a single parameter (e.g., founding time). We infer a time to the most recent common ancestor of 1.7 million years (MY) for this population. However, we show that the Yoruba SFS is not informative enough to discriminate between several different models of growth. We also show that for such simple demographies, the fit of one-parameter models outperforms the stairway plot, a recently developed model-flexible method. The use of this method on simulated data suggests that it is biased by the noise intrinsically present in the data.
Locomotion Behavior Is Affected by the GαS Pathway and the Two-Pore-Domain K+ Channel TWK-7 Interacting in GABAergic Motor Neurons in Caenorhabditis elegans
Authors: Gottschling Dieter-Christian , Döring Frank , Lüersen Kai 
Published: March 2017

Abstract
Adjusting the efficiency of movement in response to environmental cues is an essential integrative characteristic of adaptive locomotion behavior across species. However, the modulatory molecules and the pathways involved are largely unknown. Recently, we demonstrated that in Caenorhabditis elegans, a loss-of-function of the two-pore-domain potassium (K2P) channel TWK-7 causes a fast, coordinated, and persistent forward crawling behavior in which five central aspects of stimulated locomotion—velocity, direction, wave parameters, duration, and straightness—are affected. Here, we isolated the reduction-of-function allele cau1 of the C. elegans gene kin-2 in a forward genetic screen and showed that it phenocopies the locomotor activity and locomotion behavior of twk-7(null) animals. Kin-2 encodes the negative regulatory subunit of protein kinase A (KIN-1/PKA). Consistently, we found that other gain-of-function mutants of the GαS-KIN-1/PKA pathway resemble kin-2(cau1) and twk-7(null) in locomotion phenotype. Using the powerful genetics of the C. elegans system in combination with cell type-specific approaches and detailed locomotion analyses, we identified TWK-7 as a putative downstream target of the GαS-KIN-1/PKA pathway at the level of the γ-aminobutyric acid (GABA)ergic D-type motor neurons. Due to this epistatic interaction, we suggest that KIN-1/PKA and TWK-7 may share a common pathway that is probably involved in the modulation of both locomotor activity and locomotion behavior during forward crawling.
DNA Damage Tolerance Pathway Choice Through Uls1 Modulation of Srs2 SUMOylation in Saccharomyces cerevisiae
Authors: Kramarz Karol , Mucha Seweryn , Litwin Ireneusz , Barg-Wojas Anna , Wysocki Robert , Dziadkowiec Dorota 
Published: March 2017

Abstract
DNA damage tolerance and homologous recombination pathways function to bypass replication-blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates, often leading to cell death or cancer formation in higher organisms. Post-translational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis, while polyubiquitination stimulates template switching. Srs2 helicase binds to small ubiquitin-related modifier (SUMO)-modified PCNA to suppress a subset of Rad51-dependent homologous recombination. Conversely, SUMOylation of Srs2 attenuates its interaction with PCNA. Sgs1 helicase and Mus81 endonuclease are crucial for disentanglement of repair intermediates at the replication fork. Deletion of both genes is lethal and can be rescued by inactivation of Rad51-dependent homologous recombination. Here we show that Saccharomyces cerevisiae Uls1, a member of the Swi2/Snf2 family of ATPases and a SUMO-targeted ubiquitin ligase, physically interacts with both PCNA and Srs2, and promotes Srs2 binding to PCNA by downregulating Srs2-SUMO levels at replication forks. We also identify deletion of ULS1 as a suppressor of mus81Δ sgs1Δ synthetic lethality and hypothesize that uls1Δ mutation results in a partial inactivation of the homologous recombination pathway, detrimental in cells devoid of both Sgs1 and Mus81. We thus propose that Uls1 contributes to the pathway where intermediates generated at replication forks are dismantled by Srs2 bound to SUMO-PCNA. Upon ULS1 deletion, accumulating Srs2-SUMO—unable to bind PCNA—takes part in an alternative PCNA-independent recombination repair salvage pathway(s).
Bivariate Analysis of Age-Related Macular Degeneration Progression Using Genetic Risk Scores
Authors: Ding Ying , Liu Yi , Yan Qi , Fritsche Lars G , Cook Richard J , Clemons Traci , Ratnapriya Rinki , Klein Michael L , Abecasis Gonçalo R , Swaroop Anand , Chew Emily Y , Weeks Daniel E , Chen Wei ,   the AREDS2 Research Group
Published: March 2017

AbstractDing et al. used data from large clinical trials to evaluate the effects of known age-related macular generation (AMD) risk variants on disease progression...Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. While many AMD susceptibility variants have been identified, their influence on AMD progression has not been elucidated. Using data from two large clinical trials, Age-Related Eye Disease Study (AREDS) and AREDS2, we evaluated the effects of 34 known risk variants on disease progression. In doing so, we calculated the eye-level time-to-late AMD and modeled them using a bivariate survival analysis approach, appropriately accounting for between-eye correlation. We then derived a genetic risk score (GRS) based on these 34 risk variants, and analyzed its effect on AMD progression. Finally, we used the AREDS data to fit prediction models of progression based on demographic and environmental factors, eye-level AMD severity scores and the GRS and tested the models using the AREDS2 cohort. We observed that GRS was significantly associated with AMD progression in both cohorts, with a stronger effect in AREDS than in AREDS2 (AREDS: hazard ratio (HR) = 1.34, P = 1.6 × 10−22; AREDS2: HR = 1.11, P = 2.1 × 10−4). For prediction of AMD progression, addition of GRS to the demographic/environmental risk factors considerably improved the prediction performance. However, when the baseline eye-level severity scores were included as the predictors, any other risk factors including the GRS only provided small additional predictive power. Our model for predicting the disease progression risk demonstrated satisfactory performance in both cohorts, and we recommend its use with baseline AMD severity scores plus baseline age, education level, and smoking status, either with or without GRS.
Penentuan Kadar Minyak Atsiri Kulit Jeruk Sunkist (Citrus sinensis L. Osbeck) sebagai Alternatif Peluruh Sterofoam Alami
Authors: Fitrianti Annisa Eka , Dheafithraza Yockie , Handayani Nadhira , Afifah Nadiya N , Mariyam Siti 
Published: March 2017

Sterofoam banyak digunakan di segala bidang namun sifatnya yang sulit untuk diurai menjadikannya
sebagai salah satu limbah abadi. Beberapa penelitian membuktikan bahwa kandungan limonene dari
kulit jeruk sunkist (Citrus sinensis L. Osbeck) terbukti mampu meluruhkan sterofoam dengan hasil yang
cukup banyak, namun belum ditetapkan kadar yang efektif. Penelitian ini bertujuan untuk mengetahui
kadar minyak atsiri kulit jeruk sunkist terkecil yang masih efektif untuk meluruhkan sterofoam. Minyak
atsiri diisolasi dengan metode distilasi dan dekantasi, kemudian dilakukan penentuan kadar. Hasil
pengamatan menunjukkan setiap 300 gram kulit jeruk sunkist menghasilkan destilat rata-rata sebanyak
5 mL (1,67% (v/b)). Kadar minyak atsiri kulit jeruk sunkist yang efektif untuk meluruhkan sterofoam
adalah 25% dengan perbandingan minyak atsiri kulit jeruk sunkist : etanol : air adalah 1 : 1 : 2. Massa
sterofoam maksimum yang dapat diluruhkan oleh 1 mL minyak atsiri tersebut berbeda-beda tergantung
pada jenis sterofoam yang digunakan. Sterofoam yang paling banyak diluruhkan oleh kulit jeruk sunkist
25% adalah sterofoam papan pengumuman yaitu sebanyak 200 mg/mL. Minyak atsiri kulit jeruk sunkist
dapat digunakan sebagai peluruh sterofoam alami.
Pemanfaatan Selulosa Dari Limbah Jerami Padi (Oryza sativa) Sebagai Bahan Bioplastik
Authors: Pratiwi Rimadani , Rahayu Driyanti , Barliana Melisa Intan 
Published: March 2017

Jerami padi (Oryza sativa) memiliki kandungan selulosa yang cukup tinggi. Selulosa merupakan biopolimer alami yang dapat digunakan sebagai bahan bioplastik. Penelitian ini bertujuan untuk mengetahui apakah selulosa dari limbah jerami padi dapat dimanfaatkan sebagai bahan bioplastik dan bagaimana karakterisasi bioplastik yang dihasilkan dari limbah jerami padi tersebut. Penelitian ini dilakukan dalam beberapa tahapan, yaitu preparasi bahan, pembuatan pulp, pembuatan bioplastik dengan metode inversi fasa dengan variasi jumlah kitosan dan pulp selulosa 3:10, 4:10, dan 5:10, serta karakterisasi bioplastik. Bioplastik yang dihasilkan dari berbagai perbandingan pulp selulosa dan kitosan memiliki karakterisitik yang berbeda-beda. Analisis morfologi menunjukkan bahwa bioplastik yang terbentuk belum homogen dan pada analisis gugus fungsi, tidak ditemukan adanya gugus fungsi baru dalam bioplastik dibandingkan terhadap gugus fungsi yang ada pada bahan pembentuknya. Nilai penyerapan air pada bioplastik dengan perbandingan kitosan dengan pulp selulosa 3:10, 4:10 dan 5:10 adalah 154.65%, 119. 21%, dan 93.873 % . Hasil pengujian sifat mekanik yaitu kuat tarik secara berturut-turut adalah 4.2 MPa, 13.8 MPa, dan 4,1 MPa. Dari hasil penelitian dapat disimpulkan bahwa selulosa dari limbah jerami padi dapat dimanfaatkan sebagai bahan bioplastik.
Pengaruh Jenis Penyalut Terhadap Stabilitas Likopen Dalam Bentuk Sediaan Mikrokapsul
Authors: Amila Amila , Hadiansyah Cepy , Fazriah Yukeu , Darusman Fitrianti , Topik Indra 
Published: March 2017

Berbagai penelitian membuktikan bahwa likopen dapat menurunkan resiko berbagai penyakit seperti gangguan kardiovaskular, diabetes, hiperkolesterolemia dan kanker. Akan tetapi, likopen sangat mudah mengalami reaksi isomerisasi dan oksidasi selama proses pengolahan maupun penyimpanan karena memiliki banyak ikatan tak jenuh, sehingga aktivitasnya jadi menurun. Oleh sebab itu, untuk meningkatkan stabilitas likopen dilakukan teknik mikroenkapsulasi. Tujuan dari penelitan ini adalah mengetahui pengaruh jenis penyalut terhadap stabilitas likopen hasil mikroenkapsulsi dengan metode spray dry. Jenis penyalut yang digunakan adalah Hidroksi propil β-siklodekstrin (M1) dan kombinasi Whey protein-Maltodekstrin (M2). Mikrokapsul yang diperoleh dievaluasi meliputi Efisiensi Enkapsulasi (EE), kandungan lembab dan sifat organolpetis, lalu dilanjutkan dengan pengujian stabilitas pada suhu kamar dengan dua kondisi yang berbeda yaitu terpapar cahaya dan tidak terpapar cahaya. Hasil evaluasi menunjukan nilai EE untuk M1 dan M2 adalah 7,6 % dan 8,2 %, Kandungan lembab 5,4 % (M1) dan 5,09% (M2), dan semua formula menunjukan sifat organolpetis yang hampir sama yaitu berbentuk serbuk berwarna jingga dengan bau khas. Hasil uji stablitas menunjukan bahwa baik M1 maupun M2 tidak mengalami penurunan kadar selama 4 minggu penyimpanan pada tempat tidak terpapar cahaya, sedangkan pembanding dalam bentuk serbuk likopen bebas mengalami penurunan kadar sebesar 40,9%. Pada penyimpanan terpapar cahaya M1 dan M2 mengalami penurunan kadar masing masing sebesar 48,7% dan 43,37%, sedangkan pembanding 96,75%. Kesimpulan yang didapat adalah bahwa kedua jenis penyalut tidak mempengaruhi stabilitas likopen dalam bentuk mikrokapsul.
Karakterisasi Carboxymethyl Cellulose Sodium (Na-CMC) dari Selulosa Eceng Gondok (Eichhornia crassipes (Mart.) Solms.) yang Tumbuh di Daerah Jatinangor dan Lembang
Authors: Indriyati Wiwiek , Kusmawati Rembulan , Sriwidodo Sriwidodo , Hasanah Aliya Nur , Musfiroh Ida 
Published: March 2017

Eceng gondok (Eichhornia crassipes (Mart.) Solms.) berpotensi sebagai sumber bahan baku pembuatan carboxymethyl cellulose sodium (Na-CMC) karena memiliki kandungan selulosa yang tinggi. Penelitian ini dilakukan untuk mengetahui karakteristik Na-CMC serta mengetahui signifikansi perbedaan parameter WHC (Water Holding Capacity) dan OHC (Oil Holding Capacity) dari Na CMC yang disintesis dari selulosa eceng gondok yang tumbuh di Jatinangor dan Lembang. Dilakukan isolasi α-selulosa menggunakan natrium hidroksida 30%, sintesis Na-CMC melalui tahap alkalinasi menggunakan natrium hidroksida 40% dan karboksimetilasi dengan natrium monokloroasetat; penambahan crosslinker epiklorohidrin; dan karakterisasi Na-CMC berdasarkan Farmakope Indonesia, dan JECFA. Diperoleh rendemen α-selulosa hasil isolasi dari eceng gondok Jatinangor sebesar 20,80% dan Lembang sebesar 18,60% dengan kadar α-selulosa masing-masing 76,53% dan 71,35%; hasil sintesis diperoleh rendemen Na-CMC sebesar 96,87% dan 85,03%; penambahan crosslinker menghasilkan rendemen Na-CMC sebesar 439,14% dan 221,81%. Hasil karakterisasi menunjukkan bahwa Na-CMC telah memenuhi persyaratan organoleptis, kelarutan, foam test, pembentukan endapan, viskositas dan kandungan logam berat. Beberapa parameter lain seperti susut pengeringan, kandungan natrium dan derajat substitusi belum memenuhi persyaratan, namun mempunyai nilai yang lebih baik dibandingkan dengan Na-CMC baku. Uji statistika komparatif menunjukkan adanya perbedaan yang signifikan pada nilai WHC namun tidak terdapat perbedaan yang signifikan pada nilai OHC dari Na-CMC hasil sintesis dari tanaman eceng gondok yang tumbuh di Jatinangor dan Lembang.
Intratumoral Heterogeneity in Breast Cancer: A Comparison of Primary and Metastatic Breast Cancers
Authors: Shi Yu-Jie , Tsang Julia Y. S. , Ni Yun-Bi , Tse Gary M. 
Published: March 2017

Abstract
Intratumoral heterogeneity presents challenges in the management of cancer. To gain deeper insight in intratumoral heterogeneity at different levels and tumor sites for common biomarkers in breast cancers, this report examines seven cases of invasive breast cancer with multiple axillary nodal metastases and/or recurrences for immunohistochemical expression of estrogen receptors, progesterone receptors, human epidermal growth receptor 2, and Ki67 on all tissue blocks in both primary and metastatic tumors.
Knowledge, attitude and practice toward adverse drug reaction reporting among practicing clinicians at a tertiary care hospital
Authors: Todar Toshan L. , Agrawal Manju , Hishikar Rajesh , Jha Anuja , Maheshwari Basant , Joshi Usha 
Published: March 2017

Background: Pharmacovigilance has evolved as an important tool for dealing with Adverse Drug Reactions (ADRs) both in pre-marketing and post-marketing scenario. Underreporting of ADRs at our Adverse drug reaction Monitoring Centre (AMC) led us to conduct this study to assess Knowledge, Attitude and Practice (KAP) of the practicing clinicians at our tertiary care Pt. J.N.M. Medical College associated Dr. B.R.A.M. Hospital, Raipur, Chhattisgarh, India, towards ADRs reporting.Methods: This was a cross-sectional study using pretested questionnaires consisting of 29 questions related to KAP of the practicing clinicians at Pt. J.N.M. Medical College associated Dr. B.R.A.M. Hospital, Raipur towards ADRs reporting. The percentage of responders for each question was calculated. All statistical analysis was performed in Microsoft Office Excel 2007.Results: Out of 135 questionnaires distributed only 100 were considered for analysis, so the overall response rate was 74.07%. We calculated the result from the 100 responders. Overall 77% responders were aware of existence of ADR monitoring system in India, while only 40% were aware of its existence at their hospital. Only 8% responders had reported ADRs to the National Pharmacovigilance Centre and 10% to the Adverse drug reaction Monitoring Centre (AMC) at their hospital. Lack of knowledge about where, how and whom to report ADRs, lack of time, inability to decide what to report (known or unknown ADRs) and unavailability of ADR reporting form were the important factors discouraging them reporting ADRs.Conclusions: Creating awareness regarding ADR reporting through CMEs among practicing clinicians and early sensitization at medical undergraduate level for medical students may improve the current ADR reporting rate.
Case report on tuberous sclerosis
Authors: S. Zeebaish , P. Hemalatha , Y. Anusha , N. Surendra Reddy , T. S. Durga Prasad 
Published: March 2017

Tuberous sclerosis is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. Most features of tuberous sclerosis become evident only in childhood, limiting their usefulness for early diagnosis. We report a case of 3months old female child with seizures and hypo-pigmented skin lesions. The case is rare as it is documented in a family affected continuously in three generations involving four members.
Recurrent pain in right lower quadrant- chronic appendicitis versus stone in urinary tract
Authors: Srivastava Vijai Prakash , Agarwal Ajai , Agarwal Shwetank 
Published: March 2017

Background: At times, patient undergoing treatment for stone (4mm-6mm) in urinary tract beyond 6-8 weeks keeps on complaining mild, intermittent pain in RLQ, Central abdomen with nausea without urinary symptoms. In these cases, appendicectomy was performed. Post-operative relief and histopathology revealing inflammatory changes in appendix validated the procedure.Methods: This study was conducted in department of surgery of Rajshree Medical and Research Institute of Bareilly, Uttar Pradesh, India. India. 35 patients of ages between 14-65 years, mean being (39.5 years). Male female ratio being (2.5:1) who were suffering from recurrent pain in RLQ and being treated for stone in urinary tract (4-6 mm) were selected for the study. These patients were already received treatment for Urolithiasis for 6-8 weeks but proved to be of no avail. They were considered for appendicectomy. Macroscopic and microscopic results were analysed of the specimen rendered from 35 patients. Follow up results observed for complete one year.Results: On the firm belief that symptomatically these patients are more in favour of chronic appendicitis appendicectomy was performed. Post-operative relief of pain with no added morbidity or mortality provided rationale of the procedure. Histopathology of the remove specimen showed all changes pertaining to the chronic appendicitis.Conclusions: Obvious/oblivious, when patient is having both at the same time it really becomes perplexing to take the decision. Only experienced clinical skill decision taken yields positive results. Appendicectomy done in presence of small stones in urinary tract and relief patient received in present study proved the point.