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Recent Submissions

Structural basis of Nrd1-Nab3 heterodimerization. 

Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser5-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1-Nab3 chimera reveals the basis of heterodimeri...

A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth. 

Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endo...

Asthma status is associated with decreased risk of aggressive urothelial bladder cancer. 

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the ...

Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas. 

Chronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation. The orphan nuclear receptor NR5A2 pa...

TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. 

Liver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence may underlie this regenerative failure. In human acute liver disease, and...

Heart-Breaking Telomeres. 

Telomeres, the protective ends of linear chromosomes, shorten throughout an individual's lifetime. Accumulation of critically short telomeres is proposed to be a primary molecular cause of aging and age-associated diseases. Mutations in telomere maintenance genes are associated with pathologies ref...

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer. 

BACKGROUND Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibi...

CD8+ Cytotoxic Immune Infiltrate in Non-Muscle Invasive Bladder Cancer: A Standardized Methodology to Study Association with Clinico-Pathological Features and Prognosis. 

BACKGROUND Major interest lies in the evaluation of immune infiltrate in bladder cancer. CD8+ cytotoxic lymphocytes are key effectors of adaptive immune response. OBJECTIVES The aims of the study were to set up a standardized methodology for CD8+ lymphocytes estimation in NMIBC and investigate h...

Telomere shortening rate predicts species life span. 

Telomere shortening to a critical length can trigger aging and shorter life spans in mice and humans by a mechanism that involves induction of a persistent DNA damage response at chromosome ends and loss of cellular viability. However, whether telomere length is a universal determinant of species l...

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing. 

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow...

Slower rates of accumulation of DNA damage in leukocytes correlate with longer lifespans across several species of birds and mammals. 

Although there is previous evidence showing an increase in various types of DNA damage with aging in mice and humans, a comparative study determining accumulation rates of DNA double strand breaks, as determined by presence of phosphorylated histone H2AX (γH2AX), in leukocytes of individuals of dif...

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer. 

BACKGROUND Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. METHODS We complemented a new conventional PC GW...

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. 

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes ...

Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease. 

OBJECTIVE The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas. ...

Cell Lineage Infidelity in PDAC Progression and Therapy Resistance. 

Infidelity to cell fate occurs when differentiated cells lose their original identity and either revert to a more multipotent state or transdifferentiate into a different cell type, either within the same embryonic lineage or in an entirely different one. Whilst in certain circumstances, such as in...

Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo. 

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)-directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown...

Shorter telomere lengths in patients with severe COVID-19 disease. 

The incidence of severe manifestations of COVID-19 increases with age with older patients showing the highest mortality, suggesting that molecular pathways underlying aging contribute to the severity of COVID-19. One mechanism of aging is the progressive shortening of telomeres, which are protectiv...