News & Comment

Discovery of individualized therapies to address resistance to tyrosine kinase inhibitors (TKIs) has been hampered by the inability to test drug combinations on patient samples before and after TKI resistance. A recent study published in Science by Crystal et al. describes a methodology for pharmacological screening using a panel of 76 targeted agents and cell lines made directly from patient biopsies.

Plant reproduction is initiated by the specification of sporocytes that form haploid spores through meiosis. A new study in Arabidopsis published in Cell Research shows how the product of SPOROCYTELESS/NOZZLE, a key gene in this process, partners with co-repressors and transcription factors to promote spore formation, and draws interesting parallels with fungi.

A recent study published in Cell Research by Li and colleagues reports a detailed biophysical and structural study of AMPK's intra-molecular interactions during activation. By employing subunit tagging and proximity analysis with the aid of AlphaScreen instrumentation, Li et al. add to our understanding of the choreography of activation of AMPK by both nucleotides and phosphorylation.

Polymorphism of the FTO gene encoding an N⁶-methyladenosine (m⁶A) RNA demethylase was robustly associated with human obesity; however, the mechanism by which FTO affects metabolism, considering its emerging role in RNA modification, is still poorly understood. A new study published in Cell Research reports novel functions implicating FTO in the regulation of mRNA alternative splicing in the control of adipogenesis.

Brown or beige fat activation can cause potent anti-obesity and anti-diabetic effects. In a study recently published in Nature, Gnad et al. show that adenosine is a novel activator of brown and beige fat that acts through the A_2A receptor.

GM-CSF-producing helper T cells have previously been identified to serve a nonredundant function in the initiation of autoimmune inflammation. An article by Sheng et al. recently published by Cell Research now suggests that the differentiation program of GM-CSF-producing cells from naïve CD4⁺ T cells is distinct from that of Th1 and Th17 cells, and is regulated by the IL-7-STAT5 axis.

Cell migration is a multi-step process that involves the coordinated action of signaling networks, cytoskeletal dynamics and vesicular trafficking, leading to protrusion and adhesion at the leading edge of cells and contraction and detachment at their rear. In a recent paper in Cell Research, Ma et al. describe the biogenesis of a new exosome-like organelle — named migrasomes — that derive from retraction fibers at the rear of migrating cells and their potential roles in inter-cellular signaling.

Two articles recently published in Nature and Cell report the first transcriptome-wide maps of pseudouridine (Ψ) at single-base resolution through selective chemical labeling, suggesting new mechanisms and functions of Ψ in mRNA and non-coding RNA molecules.

Transcription is a highly regulated process and several studies have examined the role of transcription factors and various epigenetic regulators in memory formation. In a recent paper in Nature, Zokvic and colleagues show an important role for a novel regulator of chromatin structure (the incorporation of histone variants) in memory formation.

Cell-in-cell structures, also referred to as 'entosis', are frequently found in human malignancies, although their prognostic impact remains to be defined. Two articles recently published in Cell Research report the stimulation of entosis by one prominent oncogene, Kras, as well as by one class of tumor suppressors, namely epithelial cadherins E and P, illustrating the complex regulation of this biological process.

Inflammasomes are sensors that serve as activation platforms for caspase-1 — a mechanism that set the prevailing paradigm for inflammatory caspase activation. A recent Nature paper by Shi et al. upends this paradigm by describing an unprecedented model for caspase activation whereby caspase-4, -5, and -11 directly bind their agonist, cytosolic LPS, triggering auto-activation and subsequent pyroptotic cell death.