| 1. |
- Jia, Shaodong, et al.
(författare)
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Determination of deoxyribonucleoside triphosphate concentrations in yeast cells by strong anion-exchange high-performance liquid chromatography coupled with ultraviolet detection
- 2015
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Ingår i: DNA Replikation. - New York : Springer-Verlag New York. - 9781493925957 - 9781493925964 ; , s. 113-121
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Bokkapitel (refereegranskat)abstract
- DNA polymerase assays are commonly used for the detection of deoxyribonucleoside triphosphates (dNTPs) in biological samples. For better specificity and accuracy, high-performance liquid chromatography (HPLC) methods have been developed for the analysis of the four dNTPs in complex samples. Here we describe a simple method using isocratic strong anion-exchange (SAX) chromatographic separation coupled with ultraviolet detection (UV) for the analysis of the four dNTPs in budding yeast Saccharomyces cerevisiae. This method can be applied to other species of yeast or bacteria.
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| 2. |
- Ng, Bobby G., et al.
(författare)
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DPAGT1 deficiency with encephalopathy (DPAGT1-CDG) : Clinical and genetic description of 11 new patients
- 2018
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Ingår i: JIMD Reports. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 2192-8304 .- 2192-8312. ; 44, s. 85-92
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Bokkapitel (refereegranskat)abstract
- Pathogenic mutations in DPAGT1 cause a rare type of a congenital disorder of glycosylation termed DPAGT1-CDG or, alternatively, a milder version with only myasthenia known as DPAGT1-CMS. Fourteen disease-causing mutations in 28 patients from 10 families have previously been reported to cause the systemic form, DPAGT1-CDG. We here report on another 11 patients from 8 families and add 10 new mutations. Most patients have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. We also present data on three affected females that are young adults and have a somewhat milder, stable disease. Our findings expand both the molecular and clinical knowledge of previously published data but also widen the phenotypic spectrum of DPAGT1-CDG.
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| 3. |
- Swanberg, Maria, et al.
(författare)
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Animal Models of Parkinson’s Disease
- 2018
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Ingår i: Parkinson's Disease : Pathogenesis and Clinical Aspects - Pathogenesis and Clinical Aspects. - : Codon Publications. - 9780994438164 ; , s. 83-106
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Bokkapitel (refereegranskat)abstract
- Parkinson’s disease (PD) is a heterogenous disease with a varying age of onset, symptoms, and rate of progression. This heterogeneity requires the use of a variety of animal models to study different aspects of the disease. Neurotoxin-based approaches include exposure of rodents or non-human primates to 6-OHDA, MPTP, and agrochemicals such as the pesticide rotenone, the herbicide paraquat, and the fungicide maneb. Acute exposure to neurotoxins induces motor deficits and rapid nigro-striatal dopaminergic cell death by disrupting mitochondrial function and/or increasing oxidative stress, while chronic administration of neurotoxins induces progressive models which can include alpha-synuclein (α-synuclein) aggregates. Genetic-based approaches to model Parkinson’s disease include transgenic models and viral vector-mediated models based on genes linked to monogenic Parkinson’s disease, including SNCA, LRRK2, UCH-L1, PRKN, PINK1, and and DJ-1, as well as manipulation of dopaminergic transcription factors. SNCA mutations, overexpression, and introduction of α-synuclein preformed fibrils induce toxic protein aggregates and variable nigro-striatal neurodegeneration and motor deficits, depending on the specific model. Species, genetic background of a strain, and environment affect the display of symptoms and neurodegenerative hallmarks of animal models. These models can be combined to study the interplay between genetics and environment and untangle the heterogeneity and mechanisms underlying Parkinson’s disease. In this chapter, we discuss the strengths and limitations of mouse, rat, and non-human primate models of Parkinson’s disease.
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| 4. |
- Timpka, Jonathan, et al.
(författare)
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Etiology and pathogenesis of parkinson’s disease
- 2017
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Ingår i: Movement Disorders Curricula. - Vienna : Springer Vienna. - 9783709116289 - 9783709116272 ; , s. 95-101
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Bokkapitel (refereegranskat)abstract
- The etiology of Parkinson’s disease (PD) is still far from fully known. In the new millennium, an increased knowledge of the genetic forms of PD has contributed to an improved understanding of underlying cellular mechanisms that are central also in sporadic PD. Although steadily improving, the challenge to fully understand the origin, function, and consequences of Lewy bodies still remains. Toxicological or viral exposure has been hypothesized to function as stressors that, together with a genetic susceptibility, precipitate the development of PD. Meanwhile the impact of these environmental factors is somewhat controversial, it is clear that old age is the single most important risk factor for PD. The improved access to molecular genetic methods has, as in many fields of medicine, reformed PD research, and this is likely where the most significant progress will be made in the near future. Due to the heterogeneous clinical features within the PD entity and the similarities to several closely related diseases, it is reasonable to take into consideration that what is today defined as PD may not be one disease, but rather several diseases with similar clinical features.
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| 5. |
- Gustafson, Deborah R.
(författare)
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Adipose Tissue Complexities in Dyslipidemias
- 2019
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Ingår i: Dyslipidemia. - London : IntechOpen. - 9781839680045 - 9781839680038 - 9781839680052 ; , s. 1-22
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Bokkapitel (refereegranskat)abstract
- Adipose tissue is the largest organ in the human body and, in excess, contributes to dyslipidemias and the dysregulation of other vascular and metabolic processes. Adipose tissue is heterogeneous, comprised of several cell types based on morphology, cellular age, and endocrine and paracrine function. Adipose tissue depots are also regional, primarily due to sex differences and genetic variation. Adipose tissue is also characterized as subcutaneous vs. visceral. In addition, fatty deposits exist outside of adipose tissue, such as those surrounding the heart, or as infiltration of skeletal muscle. This review focuses on adipose tissue and its contribution to dyslipidemias. Dyslipidemias are defined as circulating blood lipid levels that are too high or altered. Lipids include both traditional and nontraditional species. Leaving aside traditional definitions, adipose tissue contributes to dyslipidemias in a myriad of ways. To address a small portion of this topic, we reviewed (a) adipose tissue location and cell types, (b) body composition, (c) endocrine adipose, (d) the fat-brain axis, and (e) genetic susceptibility. The influence of these complex aspects of adipose tissue on dyslipidemias and human health, illustrating that, once again, that adipose tissue is a quintessential, multifunctional tissue of the human body, will be summarized.
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| 6. |
- Schaafsma, Gerard C. P., et al.
(författare)
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Genetic Variation in Bruton Tyrosine Kinase
- 2015
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Ingår i: Agammaglobulinemia. - Cham : Springer International Publishing. - 9783319227146 ; , s. 75-85
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Bokkapitel (refereegranskat)abstract
- X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency caused by variations in the gene encoding for Bruton's tyrosine kinase (BTK). Patients with XLA have decreased numbers of mature B cells, lack all immunoglobulin isotypes, and therefore have susceptibility to severe bacterial infections. XLA-causing variations are collected into BTKbase freely available at http://structure.bmc.lu.se/idbase/BTKbase/. Details of the variations are provided at DNA, RNA, and protein levels, using standardized systematic names and a plain English description. In addition, clinical details from the patients are provided when available. BTKbase contains variation entries for 1362 patients from 1198 unrelated families altogether for 742 unique molecular events. The localization of the variations on the gene and protein for BTK can be analyzed by clicking sequences on web pages. The distribution of the variations in the five structural domains is approximately according to the length of the domains, except for the TH and SH3 domains. The most frequently affected sites are CpG dinucleotides. The majority of the amino acid substitutions are structural affecting protein fold or stability. Detailed statistics is provided highlighting variation types, affected domains, exons and introns, as well as structural consequences.
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| 7. |
- Ahuja, Satpal
(författare)
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Pioneers for the Basic Understanding of Usher syndrome
- 2011
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Ingår i: Usher syndrome: pathogenesis, diagnosis, and therapy. - 9781612092270 ; , s. 421-428
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Bokkapitel (refereegranskat)abstract
- After the first description of the inherited nature of bimodal deaf-blindness disease in mid nineteenth century by pioneering ophthalmologists Albrecht von Graefe (May 22, 1828 ± July 20, 1870) and Richard Liebreich (June 30, 1830 - January 19, 1917) followed by its confirmation in early twentieth century from a larger number of patients by another pioneer ophthalmologist Charles Howard Usher (March 02, 1865 - March 03, 1942) the pathogenesis of Usher syndrome (USH) was studied unsuccessfully by cytological methods. In 1922 aBritish geneticist Julia Bell described the phenotypic heterogeneity in deaf-blind patients and this served as a base for the standardization of USH types by S.L.H. Davenport and G.S. Omenn in 1977. To date nine causative genes and twelve chromosomal loci have been described and some of the causative genes are yet to be identified. In spite of the knowledge of the genetic heterogeneity the clinical classification of Usher syndrome into USH type 1, 2, and 3 is still used.
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| 8. |
- Benetó, Noelia, et al.
(författare)
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Genome Editing Using Cas9-gRNA Ribonucleoprotein in Human Pluripotent Stem Cells for Disease Modeling
- 2022
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer US. - 1064-3745 .- 1940-6029. ; 2549, s. 409-425
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Bokkapitel (refereegranskat)abstract
- The discovery that the CRISPR/Cas9 system could be used for genome editing purposes represented a major breakthrough in the field. This advancement has notably facilitated the introduction or correction of disease-specific mutations in healthy or disease stem cell lines respectively; therefore, easing disease modeling studies in combination with differentiation protocols. For many years, variability in the genetic background of different stem cell lines has been a major burden to specifically identify phenotypes arising uniquely from the presence of the mutation and not from differences in other genomic regions. Here, we provide a complete protocol to introduce random indels in human wild type pluripotent stem cells using CRISPR/Cas9 in order to generate clonal lines with potential pathogenic alterations in any gene of interest. In this protocol, we use transfection of a ribonucleoprotein complex to diminish the risk of off-target effects, and select clonal lines with promising indels to obtain disease induced pluripotent stem cell lines.
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| 9. |
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| 10. |
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