Institut de Recerca Biomèdica (IRB Barcelona): Recent submissions
Now showing items 41-60 of 418
A chemo-centric view of human health and disease
Efforts to compile the phenotypic effects of drugs and environmental chemicals offer the opportunity to adopt a chemo-centric view of human health that does not require detailed mechanistic information. Here we consider ...
Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function
Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we ...
Sensitive high-throughput single-cell RNA-seq reveals within-clonal transcript correlations in yeast populations
Single-cell RNA sequencing has revealed extensive cellular heterogeneity within many organisms, but few methods have been developed for microbial clonal populations. The yeast genome displays unusually dense transcript ...
Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation
We report the design of hetero-bifunctional small molecules that selectively target p38α and p38β for degradation. These proteolysis targeted chimeras (PROTACs) are based on an ATP competitive inhibitor of p38α and p38β, ...
Aberrant phase separation and nucleolar dysfunction in rare genetic diseases
Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly ...
Transcriptional regulation of multiciliated cell differentiation
Multiciliated cells (MCC) project dozens to hundreds of motile cilia from the cell surface to generate fluid flow across epithelial surfaces or turbulence to promote the transport of gametes. The MCC differentiation program ...
Size precision in insect eyes
The building of fully functional and well-proportioned individuals relies on the precise regulation of the size of each of their constituting organs. A new study unravels a mechanism that confers precision to size regulation ...
Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies
Simple Summary Rb1 is a regulator of cell cycle progression and genomic stability. This review focuses on post-translational modifications, their effect on Rb1 interactors, and their role in intracellular signaling in the ...
The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional ...
Senescence-associated morphological profiles (SAMPs): an image-based phenotypic profiling method for evaluating the inter and intra model heterogeneity of senescence
Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence ...
Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues
Pediatric cancers are rare diseases, and children without known germline predisposing conditions who develop a second malignancy during developmental ages are extremely rare. We present four such clinical cases and, through ...
Somatic and Germline Mutation Periodicity Follow the Orientation of the DNA Minor Groove around Nucleosomes
Mutation rates along the genome are highly variable and influenced by several chromatin features. Here, we addressed how nucleosomes, the most pervasive chromatin structure in eukaryotes, affect the generation of mutations. ...
Cellular senescence is immunogenic and promotes anti-tumor immunity
Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render ...
Autocrine Wingless constricts the Drosophila embryonic gut by Ca+2-mediated repolarisation of mesoderm cells
Wg/Wnt signalling-a highly conserved transduction pathway-has most commonly been found to be involved in patterning, cell fate, or cell proliferation, but less so in shaping organs or body parts. A remarkable case of the ...
Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery
Brain delivery is one of the major challenges in drug development because of the high number of patients suffering from neural diseases and the low efficiency of the treatments available. Although the blood-brain barrier ...
Human senescent fibroblasts trigger progressive lung fibrosis in mice
Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. We hypothesized that senescent human ...
Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma
A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping ...
Tumour stroma-derived lipocalin-2 promotes breast cancer metastasis
Tumour cell-secreted factors skew infiltrating immune cells towards a tumour-supporting phenotype, expressing pro-tumourigenic mediators. However, the influence of lipocalin-2 (Lcn2) on the metastatic cascade in the tumour ...
Insights into Structure-Activity Relationships of Somatostatin Analogs Containing Mesitylalanine.
The non-natural amino acid mesitylalanine (2,4,6-trimethyl-L-phenylalanine; Msa) has an electron-richer and a more conformationally restricted side-chain than that of its natural phenylalanine counterpart. Taking these ...
Dual-specificity phosphatase 1 (Dusp1) has a central role in redox homeostasis and inflammation in the mouse cochlea
Stress-activated protein kinases (SAPK) are associated with sensorineural hearing loss (SNHL) of multiple etiologies. Their activity is tightly regulated by dual-specificity phosphatase 1 (DUSP1), whose loss of function ...
