Dysregulation of club cell biology in idiopathic pulmonary fibrosis
keithOctober 5, 20200 Comments
Recent advances in synthetic biology-enabled and natural whole-cell optical biosensing of heavy metals
A large number of scientific works have been published on whole-cell heavy metal biosensing based on optical transduction. The advances in the application of biotechnological tools not only have continuously improved the sensitivity, selectivity, and detection range for biosensors but also have simultaneously unveiled new challenges and restrictions for further improvements.
This review highlights selected aspects of whole-cell biosensing of heavy metals using optical transducers. We have focused on the progress in genetic modulation in regulatory and reporter modules of recombinant plasmids that has enabled improvement of biosensor performance.
Simultaneously, an attempt has been made to present newer platforms such as microfluidics that have generated promising results and might give a new turn to the optical biosensing field.
Targeted therapies and immune checkpoint inhibitors have advanced the treatment landscape of Renal Cell Carcinoma (RCC) over the last decade. While checkpoint inhibitors have demonstrated survival benefit and are currently approved in the front-line and second-line settings, primary and secondary resistance is common.
A comprehensive understanding of the mechanisms of immune evasion in RCC is therefore critical to the development of effective combination treatment strategies. This article reviews the current understanding of the different, yet coordinated, mechanisms adopted by RCC cells to evade immune killing; summarizes various aspects of clinical translation thus far, including the currently registered RCC clinical trials exploring agents in combination with checkpoint inhibitors; and provides perspectives on the current landscape and future directions for the field.
Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control.
Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H+ export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes.
We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.
Dysregulation of club cellbiology in idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic fibrotic lung disease with an irreversible decline of lung function. “Bronchiolization”, characterized by ectopic appearance of airway epithelial cells in the alveolar regions, is one of the characteristic features in the IPF lung.
Based on the knowledge that club cells are the major epithelial secretory cells in human small airways, and their major secretory product uteroglobin (SCGB1A1) is significantly increased in both serum and epithelial lining fluid of IPF lung, we hypothesize that human airway club cells contribute to the pathogenesis of IPF.
By assessing the transcriptomes of the single cells from human lung of control donors and IPF patients, we identified two SCGB1A1+ club cell subpopulations, highly expressing MUC5B, a significant genetic risk factor strongly associatedwith IPF, and SCGB3A2, a marker heterogeneously expressed in the club cells, respectively. Interestingly, the cellular proportion of SCGB1A1+MUC5B+ club cells was significantly increased in IPF patients, and this club cell subpopulation highly expressed genes related to mucous production and immune cell chemotaxis.
In contrast, though the cellular proportion did not change, the molecular phenotype of the SCGB1A1+SCGB3A2high club cell subpopulation was significantly altered in IPF lung, with increased expression of mucins, cytokine and extracellular matrix genes. The single cell transcriptomic analysis reveals the cellular and molecular heterogeneity of club cells, and provide novel insights into the biological functions of club cells in the pathogenesis of IPF.
Description: The pAAV-RC1 vector contains the rep and cap genes required to generated recombinant AAV of serotype 1. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-1 packaging.
Description: The pAAV-RC3 vector contains the rep and cap genes required to generated recombinant AAV of serotype 3. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-3 packaging.
Description: The pAAV-RC4 vector contains the rep and cap genes required to generated recombinant AAV of serotype 4. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-4 packaging.
Description: The pAAV-RC5 vector contains the rep and cap genes required to generated recombinant AAV of serotype 5. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-5 packaging.
Description: The pAAV-RC6 vector contains the rep and cap genes required to generated recombinant AAV of serotype 6. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-6 packaging.
Description: The pAAV-DJ vector contains the rep and cap genes required to generated recombinant AAV of serotype DJ. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-DJ packaging.
Description: The pAAV-DJ/8 vector contains the rep and cap genes required to generated recombinant AAV of serotype DJ/8. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-DJ/8 packaging.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
Description: Clone your gene of interest into this AAV Expression Vector, then co-transfect along with AAV packaging vectors into a packaging host cell line such as 293AAV.
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