To be or not to be in the nucleolus

Compartmentalization has long been known to have a key role in regulation of cellular processes. By keeping enzymes and regulatory complexes in compartments where the delivery of substrate or exit of product is controlled, competing reactions can occur simultaneously in different parts of the cell. Moreover, spatial confinement facilitates the working of molecules participating in reaction chains and is crucial for coupling unfavourable with energetically favourable chemical reactions. Although in many cases intracellular compartmentalization relies on boundaries imposed by membranes, several non-membrane-bounded compartments exist in eukaryotic cells. One of these, the nucleolus, has recently attracted much attention. The emerging view is that molecular confinement in the nucleolus actively contributes to the control of cellular survival and proliferation.     

To be or not to be a hamlet pair in sympatry

Recent adaptive radiations, such as the fringillid finches on the Galapagos archipelago or the cichlid fishes in the East African Great Lakes, are invaluable model systems for evolutionary and ecological research. Puebla et al. , in this issue of Molecular Ecology , have established a group of colourful coral reef fishes from the Caribbean sea for studying the early phases of species formation in a marine adaptive radiation. It appears that local evolutionary processes are important in this system, which might have even triggered in situ speciation.     

To be or not to be toxic: aggregations in Huntington and Alzheimer disease

Insoluble aggregated proteins in Alzheimer disease and Huntington disease might not be pathogenic. Human studies have poor correlations between aggregates and clinical disease or pathology in these disorders, whereas mouse models have demonstrated that neuronal loss can occur in the absence of detectable aggregates. Furthermore, aggregates can exist in the absence of disease pathology in mice or symptoms in humans. Recent research suggests that soluble protein fragments, not insoluble aggregated proteins, are the toxic species in these disorders.     

To be or not to be a good social partner?

Cooperation based in mutual benefit provides a perfect scenario to start selfish behaviors aimed to obtain greater benefit at the expense of the partner. Here we investigate if mutual benefit cooperation can be stable between individuals that cooperate with kindness (good partners) or if they will be displaced by other individuals that try to obtain more benefit with less cost (bad partners). Our model assumes an asymmetry between partners in such a way that one of them (actor) proposes the cooperation whereas the other (receiver) always accepts the offer. It also assumes that actors can choose the partner on the basis of their past experiences with the potential partners. With the help of a simple two-locus mathematical model we show that not only the gene that conditions the actor preference to choose good partners can increase in frequency but also the gene responsible of the good partner behavior.     

Focus on histone variant H2AX: To be or not to be

Phosphorylation of histone variant H2AX at serine 139, named γH2AX, has been widely used as a sensitive marker for DNA double-strand breaks (DSBs). γH2AX is required for the accumulation of many DNA damage response (DDR) proteins at DSBs. Thus it is believed to be the principal signaling protein involved in DDR and to play an important role in DNA repair. However, only mild defects in DNA damage signaling and DNA repair were observed in H2AX-deficient cells and animals. Such findings prompted us and others to explore H2AX-independent mechanisms in DNA damage response. Here, we will review recent advances in our understanding of H2AX-dependent and independent DNA damage signaling and repair pathways in mammalian cells.     

To be or not to be: The double-edged sword roles of liver progenitor cells

Given the liver's remarkable and unique regenerative capacity, researchers have long focused on liver progenitor cells (LPCs) and liver cancer stem cells (LCSCs). LPCs can differentiate into both hepatocytes and cholangiocytes. However, the mechanism underlying cell conversion and its distinct contribution to liver homeostasis and tumorigenesis remain unclear. In this review, we discuss the complicated conversions involving LPCs and LCSCs. As the critical intermediate state in malignant transformation, LPCs play double-edged sword roles. LPCs are not only involved in hepatic wound-healing responses by supplementing liver cells and bile duct cells in the damaged liver but may transform into LCSCs under dysregulation of key signaling pathways, resulting in refractory malignant liver tumors. Because LPC lineages are temporally and spatially dynamic, we discuss crucial LPC subgroups and summarize regulatory factors correlating with the trajectories of LPCs and LCSCs in the liver tumor microenvironment. This review elaborates on the double-edged sword roles of LPCs to help understand the liver's regenerative potential and tumor heterogeneity. Understanding the sources and transformations of LPCs is essential in determining how to exploit their regenerative capacity in the future.     

To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes

Flavin-dependent enzymes catalyse a wide range of reactions and, thereby, facilitate a variety of cellular processes. Among the properties that equip flavoenzymes with this chemical versatility is their reactivity towards oxygen, which shows huge variation among flavoproteins. A survey of known 3D structures of flavin-dependent oxidases and dehydrogenases and the correlation with their functional properties indicates that there are no structural rules that enable prediction of whether or how a flavoenzyme reacts with oxygen. Combinations of subtle factors such as dipole pre-organization, charge distribution, dynamics and solvation in the active centre determine the balance of interactions that control oxygen reactivity. The chemical basis of oxygen reactivity remains a puzzling problem and represents one of the challenging questions in modern flavoenzymology.     

To be or not to be a compatible solute: bioversatility of mannosylglycerate and glucosylglycerate

Mannosylglycerate (MG) is an intracellular organic solute found in some red algae, and several thermophilic bacteria and hyperthermophilic archaea. Glucosylglycerate (GG) was identified at the reducing end of a polysaccharide from mycobacteria and in a free form in a very few mesophilic bacteria and halophilic archaea. MG has a genuine role in the osmoadaptation and possibly in thermal protection of many hyper/thermophilic bacteria and archaea, but its role in red algae, where it was identified long before hyperthermophiles were even known to exist, remains to be clarified. The GG-containing polysaccharide was initially detected in Mycobacterium phlei and found to regulate fatty acid synthesis. More recently, GG has been found to be a major compatible solute under salt stress and nitrogen starvation in a few microorganisms. This review summarizes the occurrence and physiology of MG accumulation, as well as the distribution of GG, as a free solute or associated with larger macromolecules. We also focus on the recently identified pathways for the synthesis of both molecules, which were elucidated by studying hyper/thermophilic MG-accumulating organisms. The blooming era of genomics has now allowed the detection of these genes in fungi and mosses, opening a research avenue that spans the three domains of life, into the role of these two sugar derivatives.     

To be or not to be a responder in T-cell responses: ubiquitous oligopeptides in all proteins

Amino acid sequences of all proteins are essays written in the same language. Accordingly, the same set of words and phrases (oligopeptides) appear in totally unrelated proteins. The reason that only certain individuals of particular major histocompatibility complex (MHC) haplotypes can mount T-cell responses against a given antigen of pathogens is found in the fact that T-cell receptors are designed to recognize 18–20 residue-long peptide fragments sandwiched between two -helices of class I or class II MHC molecules. At this range of peptide lengths, most would appear as self, while nonselfness of the remainders are destined to be quite ambiguous, hence creating responders and nonresponders.