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In eukaryotic cells, heterochromatin is typically composed of tandem DNA repeats and plays crucial roles in gene expression and genome stability. It has been reported that silencing at individual units within tandem heterochromatin repeats exhibits a position-dependent variation. However, how the heterochromatin is organized at an individual repeat level remains poorly understood. Using a novel genetic approach, our recent study identified a conserved protein Rex1BD required for position-dependent silencing within heterochromatin repeats. We further revealed that Rex1BD interacts with the 14-3-3 protein to regulate heterochromatin silencing by linking RNAi and HDAC pathways. In this review, we discuss how Rex1BD and the 14-3-3 protein coordinate to modulate heterochromatin organization at the individual repeat level, and comment on the biological significance of the position-dependent effect in heterochromatin repeats. We also identify the knowledge gaps that still need to be unveiled in the field.

Cancer is most commonly viewed as resulting from somatic mutations enhancing proliferation and invasion. Some hypotheses further propose that these new capacities reveal a breakdown of multicellularity allowing cancer cells to escape proliferation and cooperation control mechanisms that were implemented during evolution of multicellularity. Here we critically review one such hypothesis, named “atavism,” which puts forward the idea that cancer results from the re-expression of normally repressed genes forming a program, or toolbox, inherited from unicellular or simple multicellular ancestors. This hypothesis places cancer in an interesting evolutionary perspective that has not been widely explored and deserves attention. Thinking about cancer within an evolutionary framework, especially the major transitions to multicellularity, offers particularly promising perspectives. It is therefore of the utmost important to analyze why one approach that tries to achieve this aim, the atavism hypothesis, has not so far emerged as a major theory on cancer. We outline the features of the atavism hypothesis that, would benefit from clarification and, if possible, unification.

I run the risk of getting into hot water over a few of the observations below, but I think that some thought regarding the intersection of public spending, patents, “intellectual” property, and the unnecessarily high costs of life-saving treatments might be worth it.

The following considerations were triggered by a recent Dutch article, published in the well-respected NRC newspaper, describing how the well-known scientist/politician Ronald Plasterk became a millionaire, upon selling a cancer-treatment patent he obtained.^[1] At the basis of some of the arguments over patents described in the NRC article is an interesting Nature Scientific Reports publication detailing a possible source of exclusively tumour-specific molecules.^[2] Such molecules are of course of great clinical interest as they might function as tumour-specific antigens, potentially unleashing the power of our own immune systems against malignant growths, with minimal chances of auto-immune complications. How important activating the immune system can be in fighting off cancer is illustrated by the so-called chimeric antigen receptor (CAR)-T cell therapy,^[3] and the use of antibodies against immune checkpoint proteins such as PD-1/PD-L1 and CTLA-4 to allow much more effective cancer immunotherapy.^[4] In the publication about tumour-specific molecules,^[2] the focus is on the peptides that result from frameshifts in open reading frames which could occur more often in the notoriously sloppy cancer cells. A surprisingly large number of such new, cancer cell exclusive, open reading frames can indeed be found in publicly available large data sets. This means that using the encoded peptides as antigens might help patients combat their tumours in a subtle instance of effective personalized medicine. Thus far the science.

It might surprise the reader that the article in question was accompanied by a competing interest declaration about a patent regarding a: “…method of preparing subject-specific immunogenic compositions based on a neo open-reading-frame peptide database.” The patent in question has in the meantime been sold for quite a lot of money to German biotech company CureVac. This could mean that such potentially life-saving treatment might in the future have limited accessibility, because of extra expenses involved. Call me old-fashioned but how can such a regrettable outcome be justified? Consider: (i) As I mentioned, the analysis was done using large, publicly available, data sets. (ii) All of this important, high level, bio-informatic analysis was performed by Plasterk's co-author, a civil servant employed by an academic hospital, that is, the tax-payer. Of note, this (probably old school) researcher was not involved in the pa

Dietary methionine restriction (MR) is associated with a spectrum of health-promoting benefits. Being conducive to prevention of chronic diseases and extension of life span, MR can activate integrated responses at metabolic, transcriptional, and physiological levels. However, how the mitochondria of MR influence metabolic phenotypes remains elusive. Here, we provide a summary of cellular functions of methionine metabolism and an overview of the current understanding of effector mechanisms of MR, with a focus on the aspect of mitochondria-mediated responses. We propose that mitochondria can sense and respond to MR through a modulatory role of lipoylation, a mitochondrial protein modification sensitized by MR.

The way the central nervous system (CNS) responds to diverse stimuli is contingent upon the specific brain state of the individual, including sleep and wakefulness. Despite the wealth of readout parameters and data delineating the brain states, the primary mechanisms are yet to be identified. Here we highlight the role of astrocytes, with a specific emphasis on chloride (Cl⁻) homeostasis as a modulator of brain states. Neuronal activity is regulated by the concentration of ions that determine excitability. Astrocytes, as the CNS homeostatic cells, are recognised for their proficiency in maintaining dynamic homeostasis of ions, known as ionostasis. Nevertheless, the contribution of astrocyte-driven ionostasis to the genesis of brain states or their response to sleep-inducing pharmacological agents has been overlooked. Our objective is to underscore the significance of astrocytic Cl⁻ homeostasis, elucidating how it may underlie the modulation of brain states. We endeavour to contribute to a comprehensive understanding of the interplay between astrocytes and brain states.

In addition to monocentric eukaryotes, which have a single localized centromere on each chromosome, there are holocentric species, with extended repeat-based or repeat-less centromeres distributed over the entire chromosome length. At least two types of repeat-based holocentromeres exist, one composed of many small repeat-based centromere units (small unit-type), and another one characterized by a few large centromere units (large unit-type). We hypothesize that the transposable element-mediated dispersal of hundreds of short satellite arrays formed the small centromere unit-type holocentromere in Rhynchospora pubera. The large centromere unit-type of the plant Chionographis japonica is likely a product of simultaneous DNA double-strand breaks (DSBs), which initiated the de novo formation of repeat-based holocentromeres via insertion of satellite DNA, derived from extra-chromosomal circular DNAs (eccDNAs). The number of initial DSBs along the chromosomes must be higher than the number of centromere units since only a portion of the breaks will have incorporated eccDNA at an appropriate position to serve as future centromere unit sites. Subsequently, preferential incorporation of the centromeric histone H3 variant at these positions is assumed. The identification of repeat-based holocentromeres across lineages will unveil the centromere plasticity and elucidate the mechanisms underlying the diverse formation of holocentromeres.

The compound eyes of insects exhibit stunning variation in size, structure, and function, which has allowed these animals to use their vision to adapt to a huge range of different environments and lifestyles, and evolve complex behaviors. Much of our knowledge of eye development has been learned from Drosophila, while visual adaptations and behaviors are often more striking and better understood from studies of other insects. However, recent studies in Drosophila and other insects, including bees, beetles, and butterflies, have begun to address this gap by revealing the genetic and developmental bases of differences in eye morphology and key new aspects of compound eye structure and function. Furthermore, technical advances have facilitated the generation of high-resolution connectomic data from different insect species that enhances our understanding of visual information processing, and the impact of changes in these processes on the evolution of vision and behavior. Here, we review these recent breakthroughs and propose that future integrated research from the development to function of visual systems within and among insect species represents a great opportunity to understand the remarkable diversification of insect eyes and vision.

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy-related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification.

Volatile compounds, such as nitric oxide and ethylene gas, play a vital role as signaling molecules in organisms. Ethylene is a plant hormone that regulates a wide range of plant growth, development, and responses to stress and is perceived by a family of ethylene receptors that localize in the endoplasmic reticulum. Constitutive Triple Response 1 (CTR1), a Raf-like protein kinase and a key negative regulator for ethylene responses, tethers to the ethylene receptors, but undergoes nuclear translocation upon activation of ethylene signaling. This ER-to-nucleus trafficking transforms CTR1 into a positive regulator for ethylene responses, significantly enhancing stress resilience to drought and salinity. The nuclear trafficking of CTR1 demonstrates that the spatiotemporal control of ethylene signaling is essential for stress adaptation. Understanding the mechanisms governing the spatiotemporal control of ethylene signaling elements is crucial for unraveling the system-level regulatory mechanisms that collectively fine-tune ethylene responses to optimize plant growth, development, and stress adaptation.