Institut de Recerca Biomèdica (IRB Barcelona): Enviaments recents
Ara mostrant els elements 101-120 de 418
Overcoming TGFβ-mediated immune evasion in cancer
This Review discusses the context-dependent functions of transforming growth factor-beta (TGF beta) with regard to the composition and behaviour of different cell populations in the tumour immune microenvironment, as well ...
The lysosomal proteome of senescent cells contributes to the senescence secretome
Senescent cells accumulate in tissues over time, favoring the onset and progression of multiple age-related diseases. Senescent cells present a remarkable increase in lysosomal mass and elevated autophagic activity. Here, ...
Formation of left-handed helices by C2′-fluorinated nucleic acids under physiological salt conditions
Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under ...
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 ...
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 ...
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, ...
Suppression of glycogen synthesis as a treatment for Lafora disease: Establishing the window of opportunity
Lafora disease (LD) is a fatal adolescence-onset neurodegenerative condition. The hallmark of LD is the accumulation of aberrant glycogen aggregates called Lafora bodies (LBs) in the brain and other tissues. Impeding ...
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 ...
A compendium of mutational cancer driver genes
A fundamental goal in cancer research is to understand the mechanisms of cell transformation. This is key to developing more efficient cancer detection methods and therapeutic approaches. One milestone towards this objective ...
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 ...
A genetic analysis reveals novel histone residues required for transcriptional reprogramming upon stress
Cells have the ability to sense, respond and adapt to environmental fluctuations. Stress causes a massive reorganization of the transcriptional program. Many examples of histone post-translational modifications (PTMs) have ...
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 ...
The need to implement FAIR principles in biomolecular simulations
In the Big Data era, a change of paradigm in the use of molecular dynamics is required. Trajectories should be stored under FAIR (findable, accessible, interoperable and reusable) requirements to favor its reuse by the ...
Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease
ClC-5 is a Cl-/H+ antiporter crucial for the homeostasis of the entire organism, and whose functional deficiencies cause pathologies such as Dent's disease, a rare genetic disorder that can have lethal consequences. ...
Success and Limitations of Current Force Fields for the Description of RNA–Ligand Complexes
We present a systematic assessment of the last generation of RNA force fields to reproduce the structures and dynamics of ligand−RNA complexes. Our comprehensive analysis helped not only to define the more reliable force ...
Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease
The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates, called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present ...
Membrane protein stabilization strategies for structural and functional studies
Accounting for nearly two-thirds of known druggable targets, membrane proteins are highly relevant for cell physiology and pharmacology. In this regard, the structural determination of pharmacologically relevant targets ...
Targeting Mitochondria to Control Ageing and Senescence
Ageing is accompanied by a progressive impairment of cellular function and a systemic deterioration of tissues and organs, resulting in increased vulnerability to multiple diseases. Here, we review the interplay between ...
Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming ...
