THEME 1 Human Cell Biology and Pathology

2005 ◽  
Vol 6 (sup1) ◽  
pp. 67-74
Keyword(s):  
2017 ◽  
Author(s):  
Gemma Hardman ◽  
Simon Perkins ◽  
Zheng Ruan ◽  
Natarajan Kannan ◽  
Philip Brownridge ◽  
...  

Protein phosphorylation is a ubiquitous post-translational modification (PTM) that regulates all aspects of life. To date, investigation of human cell signalling has focussed on canonical phosphorylation of serine (Ser), threonine (Thr) and tyrosine (Tyr) residues. However, mounting evidence suggests that phosphorylation of histidine also plays a central role in regulating cell biology. Phosphoproteomics workflows rely on acidic conditions for phosphopeptide enrichment, which are incompatible with the analysis of acid-labile phosphorylation such as histidine. Consequently, the extent of non-canonical phosphorylation is likely to be under-estimated. We report an Unbiased Phosphopeptide enrichment strategy based on Strong Anion Exchange (SAX) chromatography (UPAX), which permits enrichment of acid-labile phosphopeptides for characterisation by mass spectrometry. Using this approach, we identify extensive and positional phosphorylation patterns on histidine, arginine, lysine, aspartate and glutamate in human cell extracts, including 310 phosphohistidine and >1000 phospholysine sites of protein modification. Remarkably, the extent of phosphorylation on individual non-canonical residues vastly exceeds that of basal phosphotyrosine. Our study reveals the previously unappreciated diversity of protein phosphorylation in human cells, and opens up avenues for exploring roles of acid-labile phosphorylation in any proteome using mass spectrometry.


2021 ◽  
Vol 42 (3) ◽  
pp. 130
Author(s):  
Sudip Dhakal

The difficulties in performing experimental studies related to diseases of the human brain have fostered a range of disease models from highly expensive and complex animal models to simple, robust, unicellular yeast models. Yeast models have been used in numerous studies to understand Alzheimer’s disease (AD) pathogenesis and to search for drugs targeting AD. Thanks to the conservation of fundamental eukaryotic processes including ageing and the availability of appropriate technological platforms, budding yeast are a simple model eukaryote to assist with understanding human cell biology, offering a platform to study human diseases. This article aims to provide insights from yeast models on the contributions of amyloid beta, a causative agent in AD, and recent research findings on AD chemoprevention.


Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. 1401-1405 ◽  
Author(s):  
J. Gray Camp ◽  
Randall Platt ◽  
Barbara Treutlein

The cumulative activity of all of the body’s cells, with their myriad interactions, life histories, and environmental experiences, gives rise to a condition that is distinctly human and specific to each individual. It is an enduring goal to catalog our human cell types, to understand how they develop, how they vary between individuals, and how they fail in disease. Single-cell genomics has revolutionized this endeavor because sequencing-based methods provide a means to quantitatively annotate cell states on the basis of high-information content and high-throughput measurements. Together with advances in stem cell biology and gene editing, we are in the midst of a fascinating journey to understand the cellular phenotypes that compose human bodies and how the human genome is used to build and maintain each cell. Here, we will review recent advances into how single-cell genomics is being used to develop personalized phenotyping strategies that cross subcellular, cellular, and tissue scales to link our genome to our cumulative cellular phenotypes.


2021 ◽  
Vol 11 (20) ◽  
pp. 9755
Author(s):  
Yasunari Matsuzaka ◽  
Shinji Kusakawa ◽  
Yoshihiro Uesawa ◽  
Yoji Sato ◽  
Mitsutoshi Satoh

Automated detection of impurities is in demand for evaluating the quality and safety of human cell-processed therapeutic products in regenerative medicine. Deep learning (DL) is a powerful method for classifying and recognizing images in cell biology, diagnostic medicine, and other fields because it automatically extracts the features from complex cell morphologies. In the present study, we construct prediction models that recognize cancer-cell contamination in continuous long-term (four-day) cell cultures. After dividing the whole dataset into Early- and Late-stage cell images, we found that Late-stage images improved the DL performance. The performance was further improved by optimizing the DL hyperparameters (batch size and learning rate). These findings are first report for the implement of DL-based systems in disease cell-type classification of human cell-processed therapeutic products (hCTPs), that are expected to enable the rapid, automatic classification of induced pluripotent stem cells and other cell treatments for life-threatening or chronic diseases.


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