26,485 results
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2. Scientific Papers Have Various Structures
- Author
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Hardcastle, Valerie Gray
- Published
- 1999
3. Second blocked flu paper released
- Author
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Saey, Tina Hesman
- Published
- 2012
4. A Biometrics Invited Paper with Discussion. Sampling Strategies for Distances between DNA Sequences
- Author
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Weir, B. S. and Basten, C. J.
- Published
- 1990
- Full Text
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5. Fisher's historic 1922 paper On the dominance ratio.
- Author
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Charlesworth, Brian
- Subjects
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GENETICS , *GENETIC mutation , *GENETIC carriers , *GENES , *PROBABILITY theory , *MEDICAL research - Abstract
R.A. Fisher's 1922 paper On the dominance ratio has a strong claim to be the foundation paper for modern population genetics. It greatly influenced subsequent work by Haldane and Wright, and contributed 3 major innovations to the study of evolution at the genetic level. First, the introduction of a general model of selection at a single locus, which showed how variability could be maintained by heterozygote advantage. Second, the use of the branching process approach to show that a beneficial mutation has a substantial chance of loss from the population, even when the population size is extremely large. Third, the invention of the concept of a probability distribution of allele frequency, caused by random sampling of allele frequencies due to finite population size, and the first use of a diffusion equation to investigate the properties of such a distribution. Although Fisher was motivated by an inference that later turned out to lack strong empirical support (a substantial contribution of dominance to quantitative trait variability), and his use of a diffusion equation was marred by a technical mistake, the paper introduced concepts and methods that pervade much subsequent work in population genetics. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
6. Metapopulation dynamics in the rock-paper-scissors game with mutation: Effects of time-varying migration paths.
- Author
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Nagatani, Takashi, Ichinose, Genki, and Tainaka, Kei-ichi
- Subjects
- *
METAPOPULATION (Ecology) , *GENETIC mutation , *ROCK-paper-scissors (Game) , *TIME-varying systems , *REACTION-diffusion equations - Abstract
Highlights • We considered the effects of time-varying migration path on the metapopulation rock-paper-scissors game. • The dynamics are represented by the reaction-diffusion equations with time-dependent diffusion coefficients in diffusively coupled reactors. • We numerically obtained the solutions of the time-dependent reaction-diffusion-equations. • We found that phase transitions occur by varying a mutation rate. • The phase transitions depend highly on the frequency change of migration path. Abstract Migration paths of animals are rarely the same. The paths may change according to seasonal and circadian rhythms. We study the effect of temporal migration on population dynamics of rock-paper-scissors (RPS) games with mutation by using the metapopulation dynamic model with two patches. Via mutation, an individual R changes to S with rate μ. All agents move by random walk between two patches and the RPS game is performed in each patch. The migration path between two patches is switched on or off periodically. The dynamics are represented by the reaction-diffusion equations with time-dependent diffusion coefficients in diffusively coupled reactors. We obtain the solutions of time-dependent reaction-diffusion equations numerically and analytically. The time-varying migration path induces complex behavior for the RPS dynamics, depending on the frequency of the periodical path. We find that the phase transitions occur by varying mutation rate μ. The phase transition depends highly on the frequency. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
7. Machine learning methods for prediction of cancer driver genes: a survey paper.
- Author
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Andrades, Renan and Recamonde-Mendoza, Mariana
- Subjects
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CANCER genes , *SOMATIC mutation , *DEEP learning , *GENETIC mutation , *MACHINE learning , *THERAPEUTICS , *DIAGNOSIS , *SCIENTIFIC community - Abstract
Identifying the genes and mutations that drive the emergence of tumors is a critical step to improving our understanding of cancer and identifying new directions for disease diagnosis and treatment. Despite the large volume of genomics data, the precise detection of driver mutations and their carrying genes, known as cancer driver genes, from the millions of possible somatic mutations remains a challenge. Computational methods play an increasingly important role in discovering genomic patterns associated with cancer drivers and developing predictive models to identify these elements. Machine learning (ML), including deep learning, has been the engine behind many of these efforts and provides excellent opportunities for tackling remaining gaps in the field. Thus, this survey aims to perform a comprehensive analysis of ML-based computational approaches to identify cancer driver mutations and genes, providing an integrated, panoramic view of the broad data and algorithmic landscape within this scientific problem. We discuss how the interactions among data types and ML algorithms have been explored in previous solutions and outline current analytical limitations that deserve further attention from the scientific community. We hope that by helping readers become more familiar with significant developments in the field brought by ML, we may inspire new researchers to address open problems and advance our knowledge towards cancer driver discovery. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Clonal selection prevents tragedy of the commons when neighbors compete in a rock-paper-scissors game.
- Author
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Juul, Jeppe, Sneppen, Kim, and Mathiesen, Joachim
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CLONAL selection theory , *ROCK-paper-scissors (Game) , *BIOTIC communities , *AQUATIC ecology , *GENETIC mutation , *PREDATORY animals - Abstract
The rock-paper-scissors game is a model example of the ongoing cyclic turnover typical of many ecosystems, ranging from the terrestrial and aquatic to the microbial. Here we explore the evolution of a rock-paper-scissors system where three species compete for space. The species are allowed to mutate and change the speed by which they invade one another. In the case when all species have similar mutation rates, we observe a perpetual arms race where no single species prevails. When only two species mutate, their aggressions increase indefinitely until the ecosystem collapses and only the nonmutating species survives. Finally we show that when only one species mutates, group selection removes individual predators with the fastest growth rates, causing the growth rate of the species to stabilize. We explain this group selection quantitatively. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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9. Comments on the Paper by Wickliffe et al. (Radiat. Res. 159, 458-464, 2003)
- Author
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Dubrova, Yuri E.
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- 2003
10. Rock-paper-scissors: Engineered population dynamics increase genetic stability.
- Author
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Liao, Michael J., Din, M. Omar, Tsimring, Lev, and Hasty, Jeff
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GENE regulatory networks , *POPULATION dynamics , *GENETIC mutation , *ESCHERICHIA coli , *MICROFLUIDIC devices , *CELL culture - Abstract
Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most applications is the presence of selective pressures that lead to high mutation rates for engineered bacteria. A common strategy is to develop cloning technologies aimed at increasing the fixation time for deleterious mutations in single cells. We adopt a complementary approach that is guided by ecological interactions, whereby cyclical population control is engineered to stabilize the functionality of intracellular gene circuits. Three strains of Escherichia coli were designed such that each strain could kill or be killed by one of the other two strains. The resulting “rock-paper-scissors” dynamic demonstrates rapid cycling of strains in microfluidic devices and leads to an increase in the stability of gene circuit functionality in cell culture. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
11. Metapopulation model for rock–paper–scissors game: Mutation affects paradoxical impacts.
- Author
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Nagatani, Takashi, Ichinose, Genki, and Tainaka, Kei-ichi
- Subjects
- *
METAPOPULATION (Ecology) , *GENETIC mutation , *ROCKS , *SCISSORS & shears , *PAPER , *COEXISTENCE of species , *POPULATION research - Abstract
The rock–paper–scissors (RPS) game is known as one of the simplest cyclic dominance models. This game is key to understanding biodiversity. Three species, rock ( R ), paper ( P ) and scissors ( S ), can coexist in nature. In the present paper, we first present a metapopulation model for RPS game with mutation. Only mutation from R to S is allowed. The total population consists of spatially separated patches, and the mutation occurs in particular patches. We present reaction–diffusion equations which have two terms: reaction and migration terms. The former represents the RPS game with mutation, while the latter corresponds to random walk. The basic equations are solved analytically and numerically. It is found that the mutation induces one of three phases: the stable coexistence of three species, the stable phase of two species, and a single-species phase. The phase transitions among three phases occur by varying the mutation rate. We find the conditions for coexistence are largely changed depending on metapopulation models. We also find that the mutation induces different paradoxes in different patches. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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12. The Influence of Mobility Rate on Spiral Waves in Spatial Rock-Paper-Scissors Games.
- Author
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Mobilia, Mauro, Rucklidge, Alastair M., and Szczesny, Bartosz
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GENETIC mutation , *SIMULATION methods & models , *EQUATIONS - Abstract
We consider a two-dimensional model of three species in rock-paper-scissors competition and study the self-organisation of the population into fascinating spiraling patterns. Within our individual-based metapopulation formulation, the population composition changes due to cyclic dominance (dominance-removal and dominance-replacement), mutations, and pair-exchange of neighboring individuals. Here, we study the influence of mobility on the emerging patterns and investigate when the pair-exchange rate is responsible for spiral waves to become elusive in stochastic lattice simulations. In particular, we show that the spiral waves predicted by the system's deterministic partial equations are found in lattice simulations only within a finite range of the mobility rate. We also report that in the absence of mutations and dominance-replacement, the resulting spiraling patterns are subject to convective instability and far-field breakup at low mobility rate. Possible applications of these resolution and far-field breakup phenomena are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
13. Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation.
- Author
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Panpradist, Nuttada, Beck, Ingrid A., Chung, Michael H., Kiarie, James N., Frenkel, Lisa M., and Lutz, Barry R.
- Subjects
HIV infections ,THERAPEUTICS ,DRUG resistance in microorganisms ,OLIGONUCLEOTIDES ,ANTIRETROVIRAL agents ,LIGATURE (Surgery) ,GENOTYPES ,GENETIC mutation - Abstract
Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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14. An Updated Mutation Spectrum of the ?-Secretase Complex: Novel NCSTN Gene Mutation in an Indian Family with Hidradenitis Suppurativa and Acne Conglobata.
- Author
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Ratnamala, Uppala, Jain, Nayan K., Jhala, Devendrasinh D., Prasad, Pullabatla V. S., Saiyed, Nazia, Nair, Sreelatha, and Radhakrishna, Uppala
- Subjects
ACNE ,GENETIC mutation ,PAPER chromatography ,PROTEOLYTIC enzymes ,GENETIC testing ,MEDICAL genetics ,HIDRADENITIS suppurativa ,SPECTRUM analysis ,LONGITUDINAL method - Abstract
Background: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown to possess such mutations. HS has high genetic heterogeneity and is thought to be triggered by a combination of genetics and environmental factors. Aims: The study aimed to investigate the genetic causes of HS in a large cohort of patients and to update the mutation spectrum of γ-secretase complex genes. Methods: We conducted mutational screening of 95 sporadic HS cases and one large family with both HS and acne conglobata (AC) to identify mutations in the coding and splice junction region of γ-secretase complex genes (nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN), and aph-1 homolog B, gamma-secretase subunit (APH1B)). Results: Our study identified a nucleotide substitution of 1876C>T in the NCSTN gene, which caused a stop codon (p. Arg626X) in the affected members of a large family with HS and AC. No pathogenic variants were detected in 95 sporadic cases of HS, indicating there is possible genetic heterogeneity. Conclusion: We report a new family with a nonsense mutation in the NCSTN gene that supports the role of the γ-secretase complex genes in HS with AC. The updated γ-secretase mutation spectrum for HS now includes 78 mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
15. Nutritional Status of Sickle Cell Disease Patients: A Literature Review.
- Author
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Minjoon Hur
- Subjects
SICKLE cell anemia ,NUTRITIONAL status ,GENETIC code ,GENETIC mutation ,DISEASE prevalence - Abstract
Sickle cell disease (SCD) is a lethal, life-long condition characterized by a mutation in the gene that codes for hemoglobin. To alleviate the pain experienced by sickle cell (SC) patients, adequate nutrition levels are vital as deficiencies of vitamins or minerals may cause other symptoms. This review aims to provide an overview of the nutrient status of SC patients and propose research areas where further study is required. The review summarizes twelve primary research papers that assessed the levels of vitamins A, C, D, E, B-2, B-6, B-12, folate, magnesium, iron, zinc, and copper in SC patients. Most SC patients exhibited suboptimal levels of vitamin A, while deficiencies in vitamin D and B-2 were prevalent. Their zinc and vitamins B-6, B-12, C, and E levels were generally adequate, while elevated folate and copper levels were observed. The magnesium levels in SC patients were lower than those in the healthy population. Determining the status of iron concentration in SC patients was challenging due to the limitations associated with the measurement methods employed in the reviewed papers. There were notable differences in some of the measurement methods used for the same nutrient levels. More research is needed to find the optimal amount of vitamin A supplement for SC patients. The effect of zinc supplementation on copper levels and the cause of low zinc levels in SC patients remains unexplored. [ABSTRACT FROM AUTHOR]
- Published
- 2023
16. A LAMP-SNP Assay Detecting C580Y Mutation in Pfkelch13 Gene from Clinically Dried Blood Spot Samples.
- Author
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Khammanee, Thunchanok, Sawangjaroen, Nongyao, Buncherd, Hansuk, Aung Win Tun, and Thanapongpichat, Supinya
- Subjects
BLOOD sampling ,GENETIC mutation ,BLOOD collection ,ARTEMISININ ,FILTER paper ,MALARIA - Abstract
Artemisinin resistance (ART) has been confirmed in Greater Mekong Sub-region countries. Currently, C580Y mutation on Pfkelch13 gene is known as the molecular marker for the detection of ART. Rapid and accurate detection of ART in field study is essential to guide malaria containment and elimination interventions. A simple method for collection of malaria-infected blood is to spot the blood on filter paper and is fast and easy for transportation and storage in the field study. This study aims to evaluate LAMP-SNP assay for C580Y mutation detection by introducing an extra mismatched nucleotide at the 3' end of the FIP primer. The LAMP-SNP assay was performed in a water bath held at a temperature of 56°C for 45 min. LAMP-SNP products were interpreted by both gel-electrophoresis and HNB-visualized changes in color. The method was then tested with 120 P. falciparum DNA from dried blood spot samples. In comparing the LAMP-SNP assay results with those from DNA sequencing of the clinical samples, the 2 results fully agreed to detect C580Y. The sensitivity and specificity of the LAMP-SNP assay showed 100%. There were no cross-reactions with other Plasmodium species and other Pfkelch13 mutations. The LAMP-SNP assay performed in this study was rapid, reliable, and useful in detecting artemisinin resistance in the field study. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
17. OECD Detailed Review Paper (DRP) number 31 on “Cell Transformation Assays for Detection of Chemical Carcinogens”: main results and conclusions
- Author
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Vasseur, Paule and Lasne, Claude
- Subjects
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CELL transformation , *CARCINOGEN dose-response relationship , *GENETIC toxicology , *KINASES , *GENETIC mutation , *MAMMALIAN cell cycle , *HYPOXANTHINE phosphoribosyltransferase , *LABORATORY mice - Abstract
Abstract: The Detailed Review Paper (DRP) number 31 of the Organisation for Economic Co-operation and Development (OECD) analyses the performance of the three models used in Cell Transformation Assays (CTAs) to screen the carcinogenic potential of chemicals: the Syrian hamster embryo (SHE) cells, and the mouse cell lines BALB/c 3T3 and C3H10T1/2. The CTA results have been compared to results from recent genotoxicity tests using mammalian and non-mammalian cell systems. The performance of the CTAs in predicting carcinogenic potential has been established on several hundreds of chemicals, comprising organic and inorganic substances. The results have been analysed and the chemicals classified as rodent and/or human carcinogens. Based on this comparison and on their performance – concordance, sensitivity, specificity, positive and negative predictive capacity, and evidence for intra- and inter-laboratory reproducibility – OECD recommended that the CTAs using the SHE cells (carried out at physiological or acidic pH) and the BALB/c 3T3 cell line should be developed into OECD test guidelines. The CTA using the C3H10T1/2 cell line was considered to be useful to elucidate molecular mechanisms of cell transformation at the genomic and transcriptomic level. However, due to the limited data available on reproducibility, a test guideline was not recommended at that time. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
18. Pick Your Poisson: An Educational Primer for Luria and Delbrück's Classic Paper.
- Author
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Meneely, Philip M.
- Subjects
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GENETIC mutation , *ESCHERICHIA coli , *IMMUNITY , *GENETIC research - Abstract
The origin of beneficial mutations is fundamentally important in understanding the processes by which natural selection works. Using phage-resistant mutants in Escherichia coli as their model for identifying the origin of beneficial mutations, Luria and Delbrück distinguished between two different hypotheses. Under the first hypothesis, which they termed "acquired immunity," the phages induced bacteria to mutate to immunity; this predicts that none of the resistant mutants were present before infection by the phages. Under the second hypothesis, termed "mutation to immunity," resistant bacteria arose from random mutations independent of the presence of the phages; this predicts that resistant bacteria were present in the population before infection by the phages. These two hypotheses could be distinguished by calculating the frequencies at which resistant mutants arose in separate cultures infected at the same time and comparing these frequencies to the theoretical results under each model. The data clearly show that mutations arise at a frequency that is independent of the presence of the phages. By inference, natural selection reveals the genetic variation that is present in a population rather than inducing or causing this variation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
19. Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.
- Author
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Al-Kzayer, Lika'a, Uyen, Le, Al-Jadiry, Mazin, Al-Hadad, Salma, Al-Badri, Safaa, Ghali, Hasanein, Ameen, Najiha, Liu, Tingting, Matsuda, Kazuyuki, Abdulkadhim, Jaafar, Al-Shujairi, Tariq, Matti, Zead, Hasan, Janan, Al-Abdullah, Hussam, Al-Ani, Mouroge, Saber, Paiman, Khalil, Hisham, Inoshita, Toshi, Kamata, Minoru, and Koike, Kenichi
- Subjects
- *
ACUTE myeloid leukemia in children , *HEMATOPOIETIC stem cell transplantation , *REVERSE transcriptase polymerase chain reaction , *MOLECULAR diagnosis , *NUCLEOTIDE sequencing , *GENETIC mutation , *LEUKEMIA treatment - Abstract
The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML- RARA, RUNX1- RUNX1T1, and CBFB- MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
20. Theme 3 In Vitro Experimental Models.
- Subjects
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CONFERENCE papers , *OLIGOMERIZATION , *GENETIC mutation , *CONFERENCES & conventions , *CELL culture - Abstract
Conference papers originating from the 27th International Symposium on Amyotrophic Lateral Sclerosis (ALS) and Motor Neurone Diseases with a focus on in vitro experimental modeling are presented. The conference papers cover a range of topics which include a cellular model of ALS with SQSTM1 mutations and the oligomerization and subcellular localization of missense/in-frame deletion ALS2 mutants in cultured cells. The development of a biomolecular fluorescence complementation assay is mentioned.
- Published
- 2016
- Full Text
- View/download PDF
21. Estimation of Wilson's Disease Incidence and Carrier Frequency in the Korean Population by Screening ATP7BMajor Mutations in Newborn Filter Papers Using the SYBR Green Intercalator Method Based on the Amplification Refractory Mutation System.
- Author
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Gu-Hwan Kim, Jeong Yoon Yang, Jung-Young Park, Jin Joo Lee, Ju Hyun Kim, and Han-Wook Yoo
- Subjects
- *
HEPATOLENTICULAR degeneration , *DISEASE incidence , *GENETIC mutation , *GENETIC disorders , *MEDICAL care , *METABOLIC disorders - Abstract
Wilson's disease (WD), an autosomal recessive disorder of copper transport, is one of the most common inherited metabolic disorders in Korea. Despite its frequency, the incidence and carrier frequency of WD has not yet been estimated in the Korean population. We therefore screened for four major missense mutations (p.Arg778Leu, p.Ala874Val, p.Leu1083Phe, and p.Asn1270Ser) of the ATP7Bgene in 476 newborn filter papers by real-time multiplex PCR and melting curve analysis using the SYBR Green intercalator method based on the amplification refractory mutation system test. Newborn filter papers with abnormal melting curves were subjected to subsequent sequence analysis. Three mutated alleles, one p.Arg778Leu and two p.Ala874Val, were detected among the 476 newborn filter papers (952 alleles). The carrier frequency and incidence of WD in the Korean population were determined as 1 in 88.2 and 30,778, respectively, by reversely calculating based on the Hardy–Weinberg law. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
22. Polymorphism of the HLA-B*15 group of alleles is generated following 5 lineages of evolution † [†] The name listed for the HLA-B*15:01:01:01, -B*15:17:01:01, -B*15:30 sequences has been officially assigned as a confirmatory by the World Health Organization Nomenclature Committee. This follows the agreed policy subject to the conditions stated in the most recent nomenclature report . The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the following accession numbers: EF203076 (HLA-B*15:01:01:01), EF203077 (HLA-B*15:17:01:01), and HM106514 (HLA-B*15:30).
- Author
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Martínez-Laso, Jorge, Herraiz, Miguel Angel, Vidart, Jose Antonio, Peñaloza, Jorge, Barbolla, Maria Luz, Jurado, Maria Luisa, and Cervera, Isabel
- Subjects
- *
GENETIC polymorphisms , *HLA histocompatibility antigens , *GENE conversion , *GENETIC mutation , *PRIMATES as laboratory animals , *EXONS (Genetics) , *BIOLOGICAL evolution - Abstract
Abstract: Generation of the HLA-B*15 group of alleles has been analyzed using exon 1, intron 1, exon 2, intron 2, and exon 3 sequences from human and nonhuman primates. Results indicated that the 230 alleles analyzed could be grouped into 5 different lineages of evolution coming from nonhuman primate MHC-B* alleles sharing characteristic nucleotide sequences. The major evolutionary mechanism of evolution in this group of alleles is the gene conversion event with the exchange of genomic sequences present in other HLA-B*alleles. This evolutionary event reflects the importance of the exchanges between different genomic regions of distinct HLA-A*, -B*, or -C* alleles and only 1 group of HLA-B* alleles (B*15 in the present paper). These data also correlated with the geographic distribution of the lineages postulated and with the corresponding serologic specificities (B62, -63, -71, -72, -75, -76, and -77). In conclusion, the high degree of polymorphism of 1 group of alleles has a specific and simple pathway of evolution, which could result in new insight into the study of immune system functionality, disease association studies, and anthropological studies. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
23. Letter of response to Professor Dalgleish regarding our paper Re: Long-term evaluation of anabolic and anti-resorptive agents in adults with familial osteoporosis due to pro205ala variant of the col1a1 gene.
- Author
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Tuck, Stephen P. and Datta, Harish K.
- Subjects
OSTEOPOROSIS genetics ,DIPHOSPHONATES ,GENETIC mutation ,SEQUENCE analysis ,OSTEOPOROSIS ,GENE expression ,BONE density ,ADULTS - Published
- 2022
- Full Text
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24. Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: A consensus-based SIE, SIES, GITMO position paper.
- Author
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Barosi, Giovanni, Vannucchi, Alessandro M., De Stefano, Valerio, Pane, Fabrizio, Passamonti, Francesco, Rambaldi, Alessandro, Saglio, Giuseppe, Barbui, Tiziano, and Tura, Sante
- Subjects
- *
MYELOPROLIFERATIVE neoplasms , *THROMBOSIS , *MYELOFIBROSIS , *TUMORS , *BIOMARKERS , *MOLECULAR biology , *GENETIC mutation - Abstract
Abstract: This article presents the results of group discussion among experts from SIE, SIES and GITMO societies aimed at highlighting unmet challenges in the management of Ph-neg myeloproliferative neoplasms (MPNs). The issues analyzed were: diagnosis of prefibrotic myelofibrosis; diagnosis of Ph-neg MPNs in the setting of splanchnic vein thrombosis (SVT); management of low-risk PV and low-risk ET patients with JAK2V617F mutation; molecular biomarkers in the prognostic evaluation of myelofibrosis (MF); ruxolitinib therapy in low-risk MF; therapy in patients with SVT-associated Ph-neg MPN; indications of splenectomy in MF. For each of these issues, proposals for advancement in clinical research were addressed. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
25. Integrating image and gene-data with a semi-supervised attention model for prediction of KRAS gene mutation status in non-small cell lung cancer.
- Author
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Xue, Yuting, Zhang, Dongxu, Jia, Liye, Yang, Wanting, Zhao, Juanjuan, Qiang, Yan, Wang, Long, Qiao, Ying, and Yue, Huajie
- Subjects
RAS oncogenes ,NON-small-cell lung carcinoma ,GENETIC mutation ,SUPERVISED learning ,PREDICTION models ,COMPUTED tomography ,DATA fusion (Statistics) - Abstract
KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S
2 MMAM). S2 MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2 MF-CN). S2 MMAM facilitates the execution of the classification task by transferring the useful information captured in SMF-SN to the S2 MF-CN to improve the model prediction accuracy. In SMF-SN, we propose a Triple Attention-guided Feature Aggregation module for obtaining segmentation features that incorporate high-level semantic abstract features and low-level semantic detail features. Segmentation features provide pre-guidance and key information expansion for S2 MF-CN. S2 MF-CN shares the encoder and decoder parameters of SMF-SN, which enables S2 MF-CN to obtain rich classification features. S2 MF-CN uses the proposed Intra and Inter Mutual Guidance Attention Fusion (I2 MGAF) module to first guide segmentation and classification feature fusion to extract hidden multi-scale contextual information. I2 MGAF then guides the multidimensional fusion of genetic data and CT image data to compensate for the lack of information in single modality data. S2 MMAM achieved 83.27% AUC and 81.67% accuracy in predicting KRAS gene mutation status in NSCLC. This method uses medical image CT and genetic data to effectively improve the accuracy of predicting KRAS gene mutation status in NSCLC. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
26. Abstracts of papers presented at the 21st Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 11 November 2010.
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GREENE, NICHOLAS D. E., COPP, ANDREW J., and WARD, ANDREW
- Subjects
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GENETIC mutation , *MAMMALS , *SPINA bifida , *NEURAL tube defects , *DISEASE progression , *EPITHELIUM , *LABORATORY mice - Published
- 2011
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27. The evolution of man (a paper read before the Mendelian Society).
- Author
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Cunningham, J.T.
- Subjects
- *
BIOLOGICAL evolution , *HUMAN beings , *BIOLOGICAL adaptation , *NATURAL selection , *GENETIC mutation , *SPECIES - Abstract
The article presents information on some modern conceptions of biology related to human species. It is noted that species' adaptation to different modes of life was assumed by the Darwinian Theory. According to the author, modern school of evolutionists believes that they have not evolved by natural selection but rather arose as mutations. He suggests that one must conclude that man anthropoid apes mainly in adaptational characters, which he believes as inborn or congenital.
- Published
- 2009
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28. What the papers say: where is the somatic mutation that causes aging?
- Author
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Driver, Christopher
- Subjects
- *
ANTIBODY diversity , *GENETIC mutation , *RECOMBINANT DNA , *OXIDATIVE stress , *GENETIC engineering , *MEDICAL research - Abstract
Studies somatic mutation that causes aging by researchers from Victoria. Propositions that somatic mutations make major contributions to aging; Evidence showing a contributory role of a gene knock-in mouse for mutation in mtDNA; Indications that some GC-rich sequences in the nuclear DNA are more sensitive to oxidative damage than mtDNA.
- Published
- 2004
- Full Text
- View/download PDF
29. research paper Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.
- Author
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Hellberg, Å., Ringressi, A., Yahalom, V., Säfwenberg, J., Reid, M. E., and Olsson, M. L.
- Subjects
- *
GENETIC mutation , *BLOOD , *GENETICS , *PHENOTYPES , *DNA , *GLYCOLIPIDS - Abstract
The aim of this study was to further explore the molecular genetic bases of the clinically important but rare blood group phenotypes p, p1k and p2k by analysis of the 4-α-galactosyltransferase (Pk) and 3-β-N-acetylgalactosaminyltrans- ferase (P) genes responsible for synthesis of the related pk (Gb3) and p (Gb4) antigens respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against certain infectious agents. Blood samples from 20 p and p1k or p2k individuals of different geographic and ethnic origin were investigated. DNA sequencing by capillary electrophoresis was performed following amplification of the coding regions in the Pk or P genes. In the pk gene, nine novel and five previously described mutations were detected. One of the newly found mutations introduced an immediate stop, five shifted the reading frame introducing premature stop codons and three were missense mutations causing amino acid substitutions in conserved regions of the transferase. Four new and two previously described mutations in the P gene were found. Three of the novel alleles reported here carried nonsense mutations whilst the fourth allele had a missense mutation. The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
30. research paper FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact.
- Author
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Au, Wing Y., Alvin Fung, Chim, Chor S., Lie, Albert K., Liang, Raymond, Ma, Edmond S. K., Chan, Cheuk H., Wong, Kit F., and Kwong, Yok L.
- Subjects
- *
GENETIC mutation , *GENETICS , *POLYMERASE chain reaction , *BLOOD cells , *DNA , *MORPHOLOGY - Abstract
FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the lTD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; lTD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 lTD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 lTD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
31. research paper Prophylactic effect of recombinant factor VIIa in factor VII deficient patients.
- Author
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Mathijssen, Natascha C. J., Masereeuw, Rosalinde, Verbeek, Kitty, Lavergne, J. Maurice, Costa, Jean-Marc, Van Heerde, Waander L., and Nováková, Irena R. O.
- Subjects
- *
BLOOD plasma , *HEMORRHAGE , *PATIENTS , *GENETIC mutation , *GENETICS , *PHENOTYPES - Abstract
Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with P2 mg rVIIa two to three times a week. Patients I and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma-derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half-lives. Pharmacokinetical analysis showed rVIIa activity half-lives of 35, 50 and 54 mm for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
32. research paper Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity.
- Author
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Orfali, Karen A., Ohene-Abuakwa, Yaw, and Ball, Sarah E.
- Subjects
- *
ANEMIA , *GENETIC polymorphisms , *GENETIC mutation , *BLOOD diseases , *BONE marrow transplantation , *PATIENTS - Abstract
A detailed family study was undertaken of patients notified to the UK Diamond Blackfan Anaemia (DBA) Registry. RPS19 mutations were detected in 16 of 104 families, including two patients with deletions detected by intragenic loss of heterozygosity of tightly linked polymorphisms. In two further cases, polymorphisms were used to determine the parental allele of origin of RPS19 point mutations. A review of clinical details of patients with mutations and patients in the literature having identical or equivalent mutations revealed evidence for a genotype:phenotype correlation with respect to the prevalence of physical anomalies, and the occurrence of mild or variable haematological severity. Nine of 60 patients had a known family history of DBA. Haematological abnormalities, including raised red cell adenosine deaminase activity, were found in first-degree relatives of 16 of 51 (31%) of patients not previously considered to have familial DBA. Results of both parents and any siblings were normal in only 35 of 60 (58%) of cases, who were therefore assumed to have sporadic de novo DBA. The classical inheritance pattern for DBA is autosomal dominant; however, 12 of 60 families (20%) had more than one affected child despite normal results in both parents. These results have important implications for genetic counselling, and for the selection of potential sibling bone marrow donors. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
33. research paper Ex vivo analysis of aberrant splicing induced by two donor site mutations in PKLR of a patient with severe pyruvate kinase deficiency.
- Author
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van Wijk, Richard, van Wesel, Annet C. W., Thomas, Adri A. M., Rijksen, Gert, and van Solinge, Wouter W.
- Subjects
- *
PYRUVATE kinase , *NUCLEOTIDES , *GENETIC mutation , *ANEMIA , *INTRONS , *EXONS (Genetics) , *MESSENGER RNA - Abstract
Two single-nucleotide substitutions in PKLR constituted the molecular basis underlying pyruvate kinase (PK) deficiency in a patient with severe haemolytic anaemia. One novel mutation, IVS5+1G>A, abolished the intron 5 donor splice site. The other mutation, c.1436G>A, altered the intron 10 donor splice site consensus sequence and, moreover, encoded an R479H substitution. We studied the effects on PKLR pre-mRNA processing, using ex vivo-produced nucleated erythroid cells from the patient. Abolition of the intron 5 splice site initiated two events in the majority of transcripts: skipping of exon 5 or, surprisingly, simultaneous skipping of exon 5 and 6 (Δ5,6). Subcellular localization of transcripts suggested that no functional protein was produced by the IVS5+1A allele. The unusual Δ5,6 transcript suggests that efficient inclusion of exon 6 in wild-type PKLR mRNA depends on the presence of splice-enhancing elements in exon 5. The c.1436G>A mutation caused skipping of exon 10 but was mainly associated with a severe reduction in transcripts although these were, in general, normally processed. Accordingly, low amounts of PK were detected in nucleated erythroid cells of the patient, thus correlating with the patient's PK-deficient phenotype. Finally, several low-abundant transcripts were detected that represent the first examples of ‘leaky-splicing’ in PKLR. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
34. research paper Thalassaemia mutations within the 5′UTR of the human β-globin gene disrupt transcription.
- Author
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Sgourou, Argyro, Routledge, Samantha, Antoniou, Michael, Papachatzopoulou, Adamantia, Psiouri, Lambrini, and Athanassiadou, Aglaia
- Subjects
- *
GENETIC mutation , *GLOBIN gene expression , *GENE expression , *ERYTHROCYTE membranes , *HEMOLYTIC anemia , *NUCLEOPROTEINS - Abstract
The mechanisms by which mutations within the 5′ untranslated region (UTR) of the human β-globin gene ( HBB) cause thalassaemia are currently not well understood. We present here the first comprehensive comparative functional analysis of four ‘silent’ mutations in the human β-globin 5′UTR, namely: +10(−T), +22(G → A), +33(C → G) and +(40–43)(−AAAC), which are present in patients with β-thalassaemia intermedia. Expression of these genes under the control of the β-globin locus control region in stable transfected murine erythroleukaemia cells showed that all four mutations decreased steady state levels of mRNA to 61·6%, 68%, 85·2% and 70·6%, respectively, compared with the wildtype gene. These mutations did not interfere with either mRNA transport from the nucleus to the cytoplasm, 3′ end processing or mRNA stability. Nuclear run-on experiments demonstrated that mutations +10(−T) and +33(C → G) reduced the rate of transcription to a degree that fully accounted for the observed lower level of mRNA accumulation, suggesting a disruption of downstream promoter sequences. Interestingly, mutation +22(G → A) decreased the rate of transcription to a low degree, indicating the existence of a mechanism that acts post-transcriptionally. Generally, our data demonstrated the significance of functionally analysing mutants of this type in the presence of a full complement of transcriptional regulatory elements within a stably integrated chromatin context in an erythroid cell environment. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
35. research paper Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature.
- Author
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Yomtovian, Roslyn, Niklinski, Waldemar, Silver, Bernard, Sarode, Ravindra, and Tsai, Han-Mou
- Subjects
- *
RITUXIMAB , *THROMBOPENIC purpura , *PLASMA exchange (Therapeutics) , *GENETIC mutation , *AUTOANTIBODIES , *ANTINEOPLASTIC agents - Abstract
Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed ‘autoimmune thrombotic thrombocytopenic purpura’. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2–3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
36. research paper Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22-23 deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research.
- Author
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Bertoni, Francesco, Conconi, Annarita, Cogliatti, Sergio B., Schmitz, Shu-Fang Hsu, Ghielmini, Michele, Cerny, Thomas, Fey, Martin, Pichert, Gabriella, Bertolini, Francesco, Ponzoni, Maurilio, Baldini, Luca, Jones, Chris, Auer, Rebecca, Zucca, Emanuele, Cavalli, Franco, and Cotter, Finbarr E.
- Subjects
- *
IMMUNOGLOBULINS , *GENETIC mutation , *LYMPHOMAS , *ANTIBODY diversity , *MEDICAL genetics , *HEMATOLOGY , *GENETICS - Abstract
Mantle cell lymphoma (MCL) shares immunophenotypic and karyotypic features with chronic lymphocytic leukaemia. The latter comprises two distinct entities with prognosis dependent upon immunoglobulin heavy chain (IgH) gene mutational status and the presence of 11q deletion. We evaluated the relevance of IgH gene mutational status, IgV gene family usage and presence of 11q deletion in a series of 42 histologically reviewed classical MCL cases to determine the prognostic impact. VH3 was the most common VH family, with VH3-21 being the most frequent individual VH gene. Approximately 30% of the cases had a IgH somatic mutation rate higher than 2%, but was only higher than 4% in <10% of cases. Half of the cases had deletion of chromosome 11q21-telomere (11q21->ter), with two minimal deleted regions, at 11q22.2 and 11q23.2. There was no association between 11q loss and IgH gene somatic mutation rate; the use of VH3-21 gene could be associated with a better prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
37. A neutral theory predicts multigenic aging and increased concentrations of deleterious mutations on the mitochondrial and Y chromosomes 1,2 <FN ID="FN1"><NO>1</NO>Guest Editor: Rajindar S. Sohal</FN> <FN ID="FN2"><NO>2</NO>This article is part of a series of reviews on “Oxidative Stress and Aging.” The full list of papers may be found on the homepage of the journal.</FN>
- Author
-
Cortopassi, Gino A.
- Subjects
- *
HUMAN genome , *POPULATION genetics , *GENETIC mutation - Abstract
Population genetic forces have molded the constitution of the human genome over evolutionary time, and some of the most important parameters are the initial frequency of the allele, p, the effective population size, Ne, and the selection coefficient, s. There is considerable agreement among evolutionary gerontologists that the amplitude of −s is small for alleles that are Deleterious In Late Life (DILL), and thus DILL traits are effectively neutral and should be fixed in the human population in relationship to Ne and p. Even higher rates of fixation of deleterious mutations are predicted to occur in the two nonrecombinant genomes in humans, i.e., the Y chromosome and the mitochondrial genome, as a consequence of their lower Ne than autosomes, and the predicted higher rate of fixation of deleterious alleles on the Y may explain the reduced average life span of males vs. females. The high probability of fixation of neutral and mildly deleterious mutations in the mitochondrial genome explains in part its fast rate of evolution, the high observed frequency of mitochondrial disease in relationship to this genome’s small size, and may be the underlying reason for the transfer of mitochondrial genes over evolutionary time to the nucleus. The predicted higher concentration of deleterious mutations on the mitochondrial genome could have some leverage to cause more dysfunction than that predicted by mitochondrial gene number alone, because of the essential role of mitochondrial gene function in multisubunit complexes, the coupling of mitochondrial functions, the observation that some mtDNA sequences facilitate somatic mutation, and the likelihood of deleterious mutations either increasing the production of or the sensitivity to mitochondrial ROS. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
38. Research trends of targeted therapy for cholangiocarcinoma from 2003 to 2022: a bibliometric and visual analysis.
- Author
-
Huang, Peng, Wen, Feng, Wu, QiuJi, Zhang, PengFei, and Li, Qiu
- Subjects
BIBLIOMETRICS ,CHOLANGIOCARCINOMA ,ONCOLOGY ,GENETIC mutation ,EPIDERMAL growth factor receptors ,DATABASES - Abstract
In the past 20 years, targeted therapy for cholangiocarcinoma has attracted certain attention. There is a significant upward in papers focusing on this field. In this study, we used bibliometric and visual methods to explore the current status and future directions in cholangiocarcinoma-targeted therapy research. A total of 1057 papers published in English from 2003 to 2022 were extracted from the Web of Science Core Collection SCI-expanded database. Furthermore, Citespace, Vosviewer, and Excel 2016 were utilized to conduct bibliometric and visual analysis. The volume of annual publications has steadily increased over the past two decades. The USA has published the largest number of publications, and the Mayo Clinic acted as the dominant institution. Cancers, Frontiers in Oncology, and Hepatology were the prolific resources in this research field. Moreover, the co-cited reference analysis uncovered the landmark paper in this field. With regard to research hotspots and frontiers, the burst keywords analysis showed that growth factor receptors and pathogenesis might become the hot topics of future research. To sum up, our study displays the current research status and future directions in the targeted therapy for cholangiocarcinoma. More comprehensive and in-depth investigations should focus on critical genetic mutations and their molecular mechanisms to prompt the molecular-targeted therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. Production of β-xylanase by a Thermomyces lanuginosus MC 134 mutant on corn cobs and its application in biobleaching of bagasse pulp
- Author
-
Kumar, Kuttanpillai Santhosh, Manimaran, Ayyachamy, Permaul, Kugen, and Singh, Suren
- Subjects
- *
PAPER industry , *BAGASSE , *CORNCOBS , *XYLANASES , *BLEACHING (Chemistry) , *SUGARCANE products , *GENETIC mutation , *FERMENTATION - Abstract
Abstract: The production of hemicellulases by Thermomyces lanuginosus SK using oatspelts xylan was examined during submerged cultivation. A high level of extracellular xylanase (346±10 U ml−1) production was observed on the fifth day; however, accessory enzyme levels were low. T. lanuginosus SK was further subjected to UV and N-methyl-N-nitro-N-nitrosoguanidine mutagenesis. The T. lanuginosus MC 134 mutant showed a 1.5 fold increase in xylanase production on oatspelts xylan, compared to the wild type strain. Xylanase production was further enhanced to 3299±95 U ml−1 by using corn cobs under optimized growth conditions. A reduction in xylanase production was observed in a 5 L fermenter. Also, the biobleaching efficiency of crude xylanase was evaluated on bagasse pulp, and a brightness of 46.07±0.05% was observed with the use of 50 U of crude xylanase per gram of pulp. This brightness was 3.6 points higher than that of the untreated samples. Reducing sugars (25.78±0.14 mg g−1) and UV-absorbing lignin-derived compound values were considerably higher in xylanase-treated samples. T. lanuginosus MC 134 has a potential application in the pulp and paper industries. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
40. Analysis of PDE6G mutations in a patient with retinitis pigmentosa.
- Author
-
Liu, Xiaona, Shi, Peiyan, and Ge, Jinling
- Subjects
FRAMESHIFT mutation ,GENETIC testing ,RETINITIS pigmentosa ,DELETION mutation ,GENETIC mutation ,HYPEROPIA - Abstract
Background: Mutations in PDE6A and PDE6B are known to cause autosomal recessive RP in humans, On the other hand, mutations in PDE6G are rare but can lead to severe early-onset RP. Case presentation: An 8-year-old Chinese boy was referred to our hospital for poor vision issues. Refraction with cycloplegia showed high hyperopia with astigmatism both eyes. Funduscopic examination revealed typical bone spicule-type pigment deposits in the periphery and midperiphery. The patient was given glasses and a whole exome sequencing containing mitochondrial genes was performed. The results of genetic testing showed that there was a heterozygous frameshift mutation and a segment deletion in the proband's PDE6G gene. Analysis of the parental genes showed that frameshift mutation was inherited from the proband's mother and segment deletion from his father. Conclusions: In this paper, we give a firsthand report that the complex heterozygous mutations of PDE6G gene can causes autosomal recessiveRP (arRP), which expands the understanding of the pathogenic genes of RP. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.
- Author
-
Yan, Lei, Shi, Jia, and Zhu, Jiazuo
- Subjects
COLORECTAL cancer ,EPIGENOMICS ,CELL death ,DRUG resistance ,CARCINOGENS ,CELL analysis ,GENETIC mutation - Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies. Highlights: Colorectal cancer (CRC) is one of the leading causes of death among patients. CRC has been characterized with changes at the genetic and epigenetic factors. The molecular factors can be used as diagnostic and prognostic factors in CRC. The cell death mechanisms demonstrate dysregulation in CRC. Autophagy has aberrant activation in CRC and exerts dual function. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. The NICE search filters for treating and managing COVID-19: validation in MEDLINE and Embase (Ovid).
- Author
-
Levay, Paul and Finnegan, Amy
- Subjects
INTERNET searching ,MEDICAL information storage & retrieval systems ,REPORTING of diseases ,DESCRIPTIVE statistics ,MEDLINE ,MEDICAL records ,ACQUISITION of data ,MEMORY ,RESEARCH methodology ,GENETIC mutation ,COVID-19 ,SARS-CoV-2 - Abstract
Objective: In this paper we report how the United Kingdom's National Institute for Health and Care Excellence (NICE) search filters for treating and managing COVID-19 were validated for use in MEDLINE (Ovid) and Embase (Ovid). The objective was to achieve at least 98.9% for recall and 64% for precision. Methods: We did two tests of recall to finalize the draft search filters. We updated the data from an earlier peer-reviewed publication for the first recall test. For the second test, we collated a set of systematic reviews from Epistemonikos COVID-19 L.OVE and extracted their primary studies. We calculated precision by screening all the results retrieved by the draft search filters from a targeted sample covering 2020-23. We developed a gold-standard set to validate the search filter by using all articles available from the "Treatment and Management" subject filter in the Cochrane COVID-19 Study Register. Results: In the first recall test, both filters had 99.5% recall. In the second test, recall was 99.7% and 99.8% in MEDLINE and Embase respectively. Precision was 91.1% in a deduplicated sample of records. In validation, we found the MEDLINE filter had recall of 99.86% of the 14,625 records in the gold-standard set. The Embase filter had 99.88% recall of 19,371 records. Conclusion: We have validated search filters to identify records on treating and managing COVID-19. The filters may require subsequent updates, if new SARS-CoV-2 variants of concern or interest are discussed in future literature. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. Nobel Laureate Michael Morris Rosbash: A scientometric portrait.
- Author
-
Kumar, Mohit, Kumar, Surjeet, and Ruhela, Arun
- Subjects
NOBEL Prize winners ,CITATION indexes ,CITATION analysis ,CIRCADIAN rhythms ,GENETIC mutation ,GENETICISTS ,DROSOPHILA - Abstract
Present Study analysis 201 publications (1972-2008) of Nobel laureate Jeffrey C Hall, an American eminent scientist in geneticist. His publications received 18,896 citations and first paper was reported in Scopus in 1972, subsequently, he published 200 research papers in various journals. The collaboration coefficient of scientist is 0.89 and forty-three (43) are two authored publications, 22 are single authored, scientist has authored highest publication in decade III (1990-1999) with 81(40.30%) publications. The paper entitled "A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila" published in 'Cell' journal in 2000 has been cited highest 632 times with ranked 1 among all his publications. Study reveals out of 201 publications 193 (96.02%) papers are obtained all 18896 citations, and top 20(9.95%) publications are obtained 7566(40.04%) citations, and cited more than 200 times, scientist preferred 50 channel of communications are used to publish his research output, most publications 28(13.93%) were published in 'Genetics' (IF: 4.556) journal. [ABSTRACT FROM AUTHOR]
- Published
- 2018
44. Mutation Analysis of the pKa Modulator Residue in β-D-xylosidase from Geobacillus Thermoleovorans IT-08: Activity Adaptation to Alkaline and High-Temperature Conditions.
- Author
-
Hartanti, Lanny, Rohman, Ali, Suwandi, Ami, Dijkstra, Bauke W., Nurahman, Zeily, and Puspaningsih, Ni Nyoman Tri
- Subjects
XYLOSIDASES ,GENETIC mutation ,HIGH temperatures ,PAPER industry ,OLIGOSACCHARIDES ,ENZYME kinetics - Abstract
β-D-xylosidases are hemicellulases that catalyze the release of xylose units from short xylooligosaccharides. Their activity is the rate-limiting step in xylan hydrolysis. A major application of these enzymes is as eco-friendly biobleaching agents in the pulp and paper industry, where thermostable, alkaliphilic xylosidases are much preferred. Hence, the isolation and characterization of new thermo-alkaliphilic xylosidases from nature, or re-engineering existing ones is of importance for industrial applications. The thermophilic bacterium Geobacillus thermoleovorans IT-08 produces a meso-thermophilic β-D-xylosidase (EC 3.2.1.37), which has a unique primary structure compared to other xylosidases with only 32-35% amino acid sequence identity. Here, we describe the role of Asp121 in modulating the enzyme's pH-activity profile. Mutation of this residue into Val121 or Asn121 increased its pH optimum by 3 pH units with a significant decrease in its activities. Furthermore, all mutants showed a significant 40 °C increase in optimum temperature compared to wild-type enzyme. This study thus illustrates the importance of the p K a modulator residue Asp121 in shifting the pH- and temperature-activity profile of the enzyme. Changing Asp/Asn residues in enzymes, especially when the residue is located near the catalytic site, may be a useful strategy for adapting the enzyme to a high pH and high temperature environment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
45. Mutant Bacteriophages, Frank Macfarlane Burnet, and the Changing Nature of "Genespeak" in the 1930s
- Author
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SANKARAN, NEERAJA
- Published
- 2010
46. Laterality, heterotaxy, and isolated congenital heart defects: The genetic basis of the segmental nature of the heart.
- Author
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Putotto, Carolina, Pugnaloni, Flaminia, Unolt, Marta, Calcagni, Giulio, Versacci, Paolo, and Marino, Bruno
- Subjects
CONGENITAL heart disease ,LATERAL dominance ,ATRIUMS (Architecture) ,GENETIC mutation ,ARTERIES - Abstract
To date, the role of NODAL in normal and abnormal L-R asymmetry has been well established. In a recent paper, mutations of this gene have been reported in heterotaxy but also in transposition with D- or L-ventricular loop. The effects of NODAL and other laterality genes can be recognized separately in all three cardiac segments: for topology and septation of the atria, for ventricular looping, and for spiralization and alignment of the great arteries. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Frequency-Dependent Selection Can Lead to Evolution of High Mutation Rates
- Author
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Rosenbloom, Daniel I. S. and Allen, Benjamin
- Published
- 2014
- Full Text
- View/download PDF
48. From Seed Germination to Flowering, Light Controls Plant Development via the Pigment Phytochrome
- Author
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Chory, J., Chatterjee, M., Cook, R. K., Elich, T., Fankhauser, C., Li, J., Nagpal, P., Neff, M., Pepper, A., Poole, D., Reed, J., and Vitart, V.
- Published
- 1996
49. So Close, yet so Far: Discrepancies between Uveal and Other Melanomas. A Position Paper from UM Cure 2020.
- Author
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Rodrigues, Manuel, de Koning, Leanne, Coupland, Sarah E., Jochemsen, Aart G., Marais, Richard, Stern, Marc-Henri, Valente, André, Barnhill, Raymond, Cassoux, Nathalie, Evans, Andrew, Galloway, Iain, Jager, Martine J., Kapiteijn, Ellen, Romanowska-Dixon, Bozena, Ryll, Bettina, Roman-Roman, Sergio, and Piperno-Neumann, Sophie
- Subjects
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THERAPEUTIC use of monoclonal antibodies , *TRANSFERASES , *PROTEIN kinase inhibitors , *GENE expression , *MELANOMA , *GENETIC mutation , *ONCOLOGISTS , *PHARMACEUTICAL industry , *UVEA cancer , *ACCESS to information , *THERAPEUTICS - Abstract
Despite much progress in our understanding of uveal melanoma (UM) over the past decades, this rare tumour is still often misclassified. Although UM, like other melanomas, is very probably derived from melanocytes, it is drastically different from cutaneous melanoma and most other melanoma subtypes in terms of epidemiology, aetiology, biology and clinical features, including an intriguing metastatic hepatotropism. UM carries distinctive prognostic chromosome alterations, somatic mutations and gene expression profiles, allowing an active tailored surveillance strategy and dedicated adjuvant clinical trials. There is no standard systemic treatment for disseminated UM at present. In contrast to cutaneous melanoma, UMs are not BRAF-mutated, thus curtailing the use of B-Raf inhibitors. Although these tumours are characterised by some immune infiltrates, immune checkpoint inhibitors are rarely effective, possibly due to a low mutation burden. UM patients across the world not only face rare cancer-related issues (e.g., specific management strategies, access to information and to expert centres), but also specific UM problems, which can be exacerbated by the common misconception that it is a subtype of cutaneous melanoma. As a European Consortium dedicated to research on UM and awareness on the disease, "UM Cure 2020" participants urge medical oncologists, pharmaceutical companies, and regulatory agencies to acknowledge UM as a melanoma with specific issues, in order to accelerate the development of new therapies for patients. [ABSTRACT FROM AUTHOR]
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- 2019
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50. Editorial.
- Author
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Penhale, Bridget and Flynn, Margaret
- Subjects
OCCUPATIONAL roles ,COVID-19 ,GENETIC mutation ,SERIAL publications ,PUBLIC health ,DOMESTIC violence ,NURSES ,TRANSPORTATION - Published
- 2022
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