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The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. 

Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors

Citation: Sek K, Chen AXY, Cole T, Armitage JD, Tong J, ……… Waithman J, Parish IA, et al. Tumor site-directed A1R expression enhances CAR T cell

The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria

BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures.

Deciphering IGH rearrangement complexity and detection strategies in acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia is a highly heterogeneous malignancy characterised by various genomic alterations that influence disease progression and therapeutic outcomes. Gene fusions involving the immunoglobulin heavy chain gene represent a complex and diverse category.

Siblings of Individuals With Neurodevelopmental Conditions: Perspectives on Risk, Resiliency and Future Research Directions

Siblings of individuals with neurodevelopmental conditions (NDCs) are at increased genetic and environmental risk for poorer psychosocial and neurocognitive outcomes compared to control groups of siblings of individuals without NDCs. 

Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycle

During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is known to be activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for activation of the mtISR remain mostly unknown.

Mesothelioma survival prediction based on a six-gene transcriptomic signature

Mesothelioma is a lethal cancer. Despite promising outcomes associated with immunotherapy, durable responses remain restricted to a minority of patients, highlighting the need for improved strategies that better predict outcome. Here, we described the development of a mesothelioma-specific gene signature that accurately predicts survival. 

Genome-Guided Discovery and Heterologous Biosynthesis of Alkylresorcinols by Collaborating Highly Reducing and Type III Polyketide Synthases

Citation: Arishi AA, Holland DC, Bracegirdle J, …… Garratt LW, Mantjani L, Moggach SA, et al. Genome-Guided Discovery and Heterologous Biosynthesis

Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis

We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes, and immune cell counts from the EPIC-HIPC newborn cohort, we report that promoter methylation was negatively correlated with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. 

Multi-omic profiling reveals an RNA processing rheostat that predisposes to prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of cancer deaths. GWAS have identified variants associated with prostate cancer susceptibility; however, mechanistic and functional validation of these mutations is lacking.