This book provides a detailed narrative of the Kat River Settlement in the Eastern Cape of South Africa during the nineteenth century. The settlement was created by the British to use the Khoekhoe as ...a living barrier between the Cape Colony and the amaXhosa. It was fought over with some regularity, however, and finally broken up after some of the Khoekhoe joined the amaXhosa in their war against the colony. Nevertheless, in the time that the settlement existed, the Khoekhoe both created a fertile landscape in the valley and developed a political theology of great importance for the evolution of South Africa. They were also the subjects of - and participants in - the major debates leading to the introduction of a liberal constitution for the Cape in 1853. The history of the settlement is thus crucial in understanding the development of both colonial racism and the creation of the colony's non-racial democracy.
The purpose of this study is to compare the landslide susceptibility mapping methods of frequency ratio (FR), logistic regression and artificial neural networks (ANN) applied in the Kat County ...(Tokat—Turkey). Digital elevation model (DEM) was first constructed using GIS software. Landslide-related factors such as geology, faults, drainage system, topographical elevation, slope angle, slope aspect, topographic wetness index (TWI) and stream power index (SPI) were used in the landslide susceptibility analyses. Landslide susceptibility maps were produced from the frequency ratio, logistic regression and neural networks models, and they were then compared by means of their validations. The higher accuracies of the susceptibility maps for all three models were obtained from the comparison of the landslide susceptibility maps with the known landslide locations. However, respective area under curve (AUC) values of 0.826, 0.842 and 0.852 for frequency ratio, logistic regression and artificial neural networks showed that the map obtained from ANN model is more accurate than the other models, accuracies of all models can be evaluated relatively similar. The results obtained in this study also showed that the frequency ratio model can be used as a simple tool in assessment of landslide susceptibility when a sufficient number of data were obtained. Input process, calculations and output process are very simple and can be readily understood in the frequency ratio model, however logistic regression and neural networks require the conversion of data to ASCII or other formats. Moreover, it is also very hard to process the large amount of data in the statistical package.
Visual detection of histone acetylation in cells is highly desirable for medical diagnostics, particularly in cancer. Currently, a single substrate-indicated multi-mode visual platform has been ...developed for detecting the activity of acetyltransferase (KAT Tip60) in circulating tumor cells (CTCs) of esophageal cancer. o-Phenylenediamine (OPD) serves as a single indicator in our constructed multi-mode analytical method, where the introduction of Cu(II) stimulates a change in fluorescent/UV–vis signals and colors. However, coenzyme A (CoA), a byproduct of the acetylation process, effectively prevents the interaction between Cu(II) and OPD, and this competitive reaction is aptly associated with the KAT Tip60-domonicated acetylation process. Good linear relationships are observed between the optical signals in the multi-mode method and the logarithms of the Tip60 concentration, with detection limits of 0.0045 ng/mL (fluorescence) and 0.058 ng/mL (UV–vis), respectively, calculated as 3σ/slope. To meet the needs of smart/precision medicine, a smartphone-based visualization approach tailored to the red-green-blue (RGB) color space is developed via Cu(II)-OPD redox catalysis. This approach is successfully employed for the analysis of Tip60-indicated acetylation in CTCs of esophageal cancer. This study establishes an important foundation for advancing RGB color-based smartphone modes for actual analyses, and integrating another catalytic unit based on the single OPD substrate presents a viable strategy for analyzing other biomarkers in cancer-targeted clinical applications.
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•A visual platform for Tip60 analysis in MYST family is developed firstly.•A smartphone is further constructed for achieving on-site detection for Tip60.•The results of dual-mode method verify each other effectively.•The Cu(II)-OPD system is used for discussing the Tip60 activity in cells.•This strategy can be easily extended for the detection of other targets.
Salah satu kearifan lokal yang ada di Provinsi Jambi adalah Suku Anak Dalam (SAD) yang dikenal dengan kepandaian dalam membuat ramuan obat tradisional. Tujuan penelitian ini adalah mengidentifikasi ...tanaman obat tradisional yang dipergunakan oleh SAD di Desa Dwi Karya Bakti, Kabupaten Bungo, Provinsi Jambi. Jenis penelitian adalah deskriptif. Pengumpulan data dilakukan di Desa Dwi Karya Bakti Kecamatan Pelepat Kabupaten Bungo. Waktu penelitian pada bulan September hingga November 2023 menggunakan wawancara mendalam, observasi dan dokumentasi tanaman obat, cara meramu dan jenis penyakit yang diobati. Sampling tumbuhan obat lengkap yang representatif dari lokasi rutin informan mengambil tanaman obat. Hasil penelitian ini mengelompokkan ramuan obat menjadi 5 rumpun tanaman obat yang biasa digunakan oleh komunitas SAD di Desa Dwi Karya Bakti yaitu kelompok untuk obat batuk dan sakit tenggorokan, obat diare, penyakit-penyakit pada ibu dan anak, obat-obatan luar (bisul, sariawan dan pegal-pegal) serta obat demam. Bagian tumbuhan yang paling banyak digunakan ialah bagian daun (38%), yang paling sedikit digunakan ialah bunga (5%) dan akar (5%). Sedangkan pengolahan yang paling banyak dilakukan ialah digunakan langsung (73,50%) tanpa direbus ataupun dibakar, dan cara pengolahan yang paling sedikit adalah dengan cara direbus (10,5%). Cara penggunaan terbanyak ialah diminum (31,5%) dan dioles (31,5%), sedangkan cara penggunaan yang paling sedikit ialah dengan cara ditetes, dijadikan kalung, diikat atau dimandikan masing-masing sebesar 5%. Disarankan untuk dapat menilai keamanan dan efektivitas dari ramuan obat tradisional yang sudah digunakan untuk penelitian selanjutnya.
The enhancer factors CREB-binding protein (CBP) and p300 (also known as KAT3A and KAT3B) maintain gene expression programs through lysine acetylation of chromatin and transcriptional regulators and ...by scaffolding functions mediated by several protein-protein interaction domains. Small molecule inhibitors that target some of these domains have been developed; however, they cannot completely ablate p300/CBP function in cells. Here we describe a chemical degrader of p300/CBP, dCBP-1. Leveraging structures of ligand-bound p300/CBP domains, we use in silico modeling of ternary complex formation with the E3 ubiquitin ligase cereblon to enable degrader design. dCBP-1 is exceptionally potent at killing multiple myeloma cells and can abolish the enhancer that drives MYC oncogene expression. As an efficient degrader of this unique class of acetyltransferases, dCBP-1 is a useful tool alongside domain inhibitors for dissecting the mechanism by which these factors coordinate enhancer activity in normal and diseased cells.
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•In silico-guided design of dCBP-1, a heterobifunctional degrader of p300 and CBP•dCBP-1 hijacks the E3 ubiquitin ligase CRBN for selective degradation of p300/CBP•Degradation of p300/CBP by dCBP-1 leads to effective multiple myeloma cell killing•dCBP-1 ablates oncogenic enhancer activity driving MYC expression
Vannam et al. report the design and characterization of dCBP-1, a potent and selective heterobifunctional degrader of the acetyltransferases p300 and CBP. Using in silico modeling to enable efficient molecular design, the authors demonstrate the enhanced effects of dCBP-1 on p300/CBP activity compared with catalytic and bromodomain inhibitors.
•Solvatochromism of 2,6-Dichloro-4-nitroaniline was studied in pure and aqueous solvent mixtures.•KAT-LSER model was utilized for solvent effect analysis.•Non-linear solvatochromism and synergism was ...observed in aqueous binary mixtures.•Non-linear solvatochromism was explained by using the preferential solvation model.•Distinct contribution from the solute preferential solvation and the mixture non-ideality was detected and quantified.
In this study, the solvatochromic behavior of 2,6-dichloro para-nitroaniline (DCPNA) was investigated in a wide range of pure solvents, and binary solvent mixtures of water with ethanol, dimethyl sulfoxide, and dimethyl formamide at 298.15 K. The absorption spectrum of DCPNA in the ultraviolet–visible range exhibits a characteristic peak that shifts with changes in the solvent along the absorption wavelength. The influential factors and their roles in solvatochromism were determined through KAT-LSER analysis in pure solvents. Solvatochromism in binary solvent mixtures showed a completely non-linear trend with respect to the composition of the solution. The recently introduced preferential solvation model was utilized to model the absorbed light wavenumber in aqueous solvent mixtures. This model elucidates the separate effects of preferential solvation of DCPNA and the non-ideal behavior of aqueous solvent mixtures in the non-linearity of solvatochromism.
Kat Mülkiyetinin yönetiminde en önemli kaynak yönetim planıdır. Yönetim planının hukuki niteliği sözleşme olup tüm kat malikleri ile haleflerini bağlar. Yönetim planının tek malik tarafından veya ...yüklenici tarafından hazırlanması uygulamada sorunlara yol açmaktadır.
Bu çalışmada, yönetim planı ile diğer kat maliklerinin yönetime katılma haklarının kısıtlanması hususu üzerinde durulacak ve çözüm önerileri sunulacaktır.
The most important source in the management of the condominium is the management plan. The legal nature of the management plan is a contract and is binding on all flat owners and their successors. Preparation of the management plan by the sole owner or the contractor causes problems in practice.
In this study, the management plan and the restriction of other flat owners' rights to participate in management will be emphasized and solution suggestions will be presented.
The world of protein acetylation Drazic, Adrian; Myklebust, Line M.; Ree, Rasmus ...
Biochimica Et Biophysica Acta - Proteins And Proteomics,
October 2016, 2016-10-00, Letnik:
1864, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Acetylation is one of the major post-translational protein modifications in the cell, with manifold effects on the protein level as well as on the metabolome level. The acetyl group, donated by the ...metabolite acetyl-coenzyme A, can be co- or post-translationally attached to either the α-amino group of the N-terminus of proteins or to the ε-amino group of lysine residues. These reactions are catalyzed by various N-terminal and lysine acetyltransferases. In case of lysine acetylation, the reaction is enzymatically reversible via tightly regulated and metabolism-dependent mechanisms. The interplay between acetylation and deacetylation is crucial for many important cellular processes. In recent years, our understanding of protein acetylation has increased significantly by global proteomics analyses and in depth functional studies. This review gives a general overview of protein acetylation and the respective acetyltransferases, and focuses on the regulation of metabolic processes and physiological consequences that come along with protein acetylation.
Recent studies of N-terminal acetylation have identified new N-terminal acetyltransferases (NATs) and expanded the known functions of these enzymes beyond their roles as ribosome-associated ...co-translational modifiers. For instance, the identification of Golgi- and chloroplast-associated NATs shows that acetylation of N termini also happens post-translationally. In addition, we now appreciate that some NATs are highly specific; for example, a dedicated NAT responsible for post-translational N-terminal acetylation of actin was recently revealed. Other studies have extended NAT function beyond Nt acetylation, including functions as lysine acetyltransferases (KATs) and non-catalytic roles. Finally, emerging studies emphasize the physiological relevance of N-terminal acetylation, including roles in calorie-restriction-induced longevity and pathological α-synuclein aggregation in Parkinson’s disease. Combined, the NATs rise as multifunctional proteins, and N-terminal acetylation is gaining recognition as a major cellular regulator.
N-terminal acetylation, long considered a co-translational and static modification, recently stepped into the post-translational world, and several reports now suggest regulation and crosstalk with other modifications as well as moonlighting functions. Aksnes et al. review novel functions of N-terminal acetyltransferases, including the most recently described Nt acetylation of actin.
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The purpose is to study the dissolution behaviour for praziquantel in different solvent. The dissolution capacity within the temperature range from 273.15 K to 313.15 K was researched ...by using the isothermal equilibrium method and evaluated with the modified Apelblat equation, λh equation and Jouyban-Acree model. In pure solvents, the largest values were found in N-methyl pyrrolidone (NMP, 8.106 × 10−2 in mole fraction) at 313.15 K, and followed by cyclohexanone (5.964 × 10−2), toluene (3.842 × 10−2), acetonitrile (3.519 × 10−2), acetone (3.001 × 10−2), ethyl acetate (2.896 × 10−2), n-octanol (2.715 × 10−2), isopropanol (1.882 × 10−2) and n-hexane (4.379 × 10−2). While in mixtures of (NMP + isopropanol), the solubility capacity increased monotonically with the increase of temperature and NMP mass fraction. KAT-LSER method was applied to analyse the effect of solute–solvent intermolecular interactions on the solubility in pure solvents. More importantly, the selection of appropriate solvents for praziquantel dissolution is important to its application. Moreover, the effect of the solute–solvent intermolecular interactions on the solubility in pure and mixed solvents was discussed as well. In the following, the analysis of apparent thermodynamic analysis indicates that the dissolution is an endothermic, spontaneous and entropy driven process.
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