Institut de Recerca Biomèdica (IRB Barcelona): Recent submissions
Now showing items 1-20 of 418
Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming
Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two ...
Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers
Background Information Mitosis is crucial for the faithful transmission of genetic material, and disruptions can result in chromosomal instability (CIN), a hallmark of cancer. CIN is a known driver of tumor heterogeneity ...
Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations
Cancer driver genes can undergo positive selection for various types of genetic alterations, including gain-of-function or loss-of-function mutations and copy number alterations (CNA). We investigated the landscape of ...
DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy
Somatic cells can transform into tumors due to mutations, and the tumors further evolve towards increased aggressiveness and therapy resistance. We develop DiffInvex, a framework for identifying changes in selection acting ...
Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
BackgroundReceptor-activated SMADs trimerize with SMAD4 to regulate context-dependent target gene expression. However, the presence of a single SMAD1/5/8 binding motif in cis-regulatory elements alone does not trigger ...
Sex and smoking bias in the selection of somatic mutations in human bladder
Men are at higher risk of several cancer types than women1. For bladder cancer the risk is four times higher for reasons that are not clear2. Smoking is also a principal risk factor for several tumour types, including ...
Flexibility in PAM recognition expands DNA targeting in xCas9
xCas9 is an evolved variant of the CRISPR-Cas9 genome editing system, engineered to improve specificity and reduce undesired off-target effects. How xCas9 expands the DNA targeting capability of Cas9 by recognising a series ...
The pseudotorsional space of RNA
The characterization of the conformational landscape of the RNA backbone is rather complex due to the ability of RNA to assume a large variety of conformations. These backbone conformations can be depicted by pseudotorsional ...
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 ...
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 ...
Epigenetic loss of the endoplasmic reticulum-associated degradation inhibitor SVIP induces cancer cell metabolic reprogramming
The endoplasmic reticulum (ER) of cancer cells needs to adapt to the enhanced proteotoxic stress associated with the accumulation of unfolded, misfolded and transformation-associated proteins. One way by which tumors thrive ...
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 ...
Data-driven identification of inherent features of eukaryotic stress-responsive genes
Living organisms are continuously challenged by changes in their environment that can propagate to stresses at the cellular level, such as rapid changes in osmolarity or oxygen tension. To survive these sudden changes, ...
Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii
The treatment of some infectious diseases can currently be very challenging since the spread of multi-, extended- or pan-resistant bacteria has considerably increased over time. On ...
Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5
The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and ...
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, ...
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 ...
Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine
Background 5′-deoxy-5′-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in ...
Apoptosis, G1 Phase Stall, and Premature Differentiation Account for Low Chimeric Competence of Human and Rhesus Monkey Naive Pluripotent Stem Cells
After reprogramming to naive pluripotency, human pluripotent stem cells (PSCs) still exhibit very low ability to make interspecies chimeras. Whether this is because they are inherently devoid of the attributes of chimeric ...
