Research Highlights

Mitotic divisions achieve equal re-partition of chromosomes into daughter cells. In their recent work in Developmental Cell, Sen, Harrison et al. propose that the risk of mis-segregation in human mitotic cells is higher than previously thought and identify the existence of an early-anaphase correction mechanism. The study documents kinetochore dynamics in unprecedented detail, providing a detailed look at the events preceding loss of correct chromosomal numericity and genomic stability.

Aposematism is a prey strategy to communicate toxicity or danger to predators, often through bright colours, and over time is learned by predators. McLellan et al. report in Current Biology that association between an aposematic insect and its host plant is learned by wild birds, to the point that any insect on the plant faces a lower predation risk.

In the 1930s, philosopher John Dewey stated: “We do not learn from experience… we learn from reflecting on experience.” The question of how we learn from the consequences of our actions has been investigated for decades. When deliberating between options, it is assumed that the outcome of our choice is used as a feedback signal to learn the value of the chosen option. But what about the forgone alternative? In a recent paper, Biderman and Shohamy show that we also revise the valuation of forgone options, assuming them to be inversely related to that of chosen ones.

The accumulation of amyloid β (Aβ) in the brain is an established feature of Alzheimer’s disease, however mechanisms that regulate Aβ accumulation are not fully understood. In a recent study, Wang et al show that Aβ accumulation in neurons is tightly regulated by cholesterol production in astrocytes. This finding paves the way for future work that will establish whether the selective removal of Aβ by targeting this mechanism has therapeutic potential.

In order to maintain persistent infections, microbes that cause chronic disease have to evade detection by the human immune system. To do so, many modulate the expression of plasma membrane receptors that trigger cell signalling pathways and immune responses. Using microscopy and cell sorting techniques, Businger et al. map the morphological changes in the plasma membranes of macrophages infected by human cytomegalovirus or human immunodeficiency virus and find novel differentially expressed receptors.

Origami, the Japanese art of paper folding, has taken on new meaning for the fields of chemistry and biology. DNA origami describes the folding of DNA strands to form nanoscale structures. The ability to design and form complex structures at a nanoscale level has fuelled new ambitions of nanostructure applications in life science. These predefined shapes become base structures for the development of a higher and complex functional structure. In a recent paper, Stömmer et al., demonstrated the ability to design a macromolecular level transportation network that allows the movement of molecules at sub-molecular levels using DNA. A multi-layer DNA origami was used to build micrometer-long hollow tunnels akin to railway tunnels. An accompanying DNA piston travelled through the tunnels with constant motion. The system also accommodated the application of electric fields to fuel the motion of the pistons along the filaments simulating a nanoscale electric railway system. This could revolutionize the way molecular drug delivery systems can be perceived in the future.

Lipid nanoparticles can be used to deliver nucleic acids for gene expression modulation—but getting them to target specific tissues is an ongoing challenge. In a new study by Dammes et al., a conformation-sensitive targeting strategy is used to achieve better selectivity in silencing gut-homing leukocytes in mouse models of colitis.

Glycans are a major composition of the cell surface that interacts with the surrounding environment. The ability to carry out glycan-binding profile studies has been mainly done with glycan arrays. However, glycan arrays are not easily adaptable for cell surface and in vivo glycan recognition assays. The Liquid Glycan Array (LiGA) reported recently by Sojitra et al. is an alternative glycan recognition assay that employs DNA barcoding, bioorthogonal ligation and deep sequencing technology. In LiGA, barcoded M13 virions are used to present glycans to allow rapid identification of binding partners based on sequence identity. This physical link between the glycan to the DNA sequence fitted in the phage genome provides an ingenious approach to maneuver glycan binding profile studies in various conditions.

While reforestation efforts are important in limiting the progression of climate change, tree stems are known to emit the potent greenhouse gas, methane. Luke Jeffrey and colleagues recently discovered that methanotrophic bacteria colonize the bark of the common lowland tree, Melaleuca quinquenervia, and significantly reduce its methane emissions. Their results expand the known pool of habitats for methanotrophic bacteria and suggest that these bark-dwelling taxa may be a future target for limiting methane emissions from trees.

Somatic mutations in cancer genomes can be caused by many different mutational processes, each of which produce distinctive patterns termed “mutational signatures”. Although cancer researchers can now recognize a large number of mutational signatures, exactly how these patterns arise remains unknown. Nik-Zainal and colleagues tackled this problem using a CRISPR-Cas9 genome editing screen to knock out components of the DNA mismatch repair machinery and learn their unique mutational patterns. Based on their data, the authors developed MMRDetect, a computational algorithm to classify the different DNA repair deficiencies and predict tumour responsiveness to immunotherapy.

There is a continual need to develop new therapies for neuropsychiatric disorders such as Schizophrenia, and identifying the underlying molecular processes remains challenging. Chadha et al. recently discovered a potential role for mTOR kinase activity disruption in Schizophrenia and further uncover the precise pathomechanism. Their study sheds further light on the role of mTOR in Schizophrenia and could inform the development of future therapeutic strategies for the condition.

Shortly after the onset of ciliogenesis in Caenorhabditis elegans sensory neurons, the centrioles/basal bodies undergo degeneration. The fate of the pericentriolar material (PCM) that was associated with those centrioles has, however, remained unknown. Two recent studies by the Dammermann and the Feldman groups now show that not only does the PCM persist at the ciliary base, it also continues to assemble in the absence of canonical centrioles. Importantly, these neuronal centrosomes retain the ability to function as the cell’s main microtubule-organizing center and support ciliary function.

Conrad Waddington famously used his epigenetic landscape to describe the paths a cell might take during developmental differentiation. In this analogy, the undifferentiated stem cell begins at the highest elevation and proceeds to tumble downward towards its final resting place, representing terminal differentiation. This general concept elegantly captures the essence of developmental transitions, but recent single-cell studies by Dr. Joanna Wysocka’s research group indicate that an alternative strategy underlies development of cranial neural crest cells. Published in Science, Antoine Zalc, Rahul Sinha and colleagues discovered that ectoderm-derived cranial neural crest cells undergo a developmental reprogramming event in vivo, expanding their differentiation potential through the reactivation of pluripotency, in effect rolling backwards up Waddington’s development landscape before eventually differentiating into mesenchymal lineages.

Recent advances in sequencing and barcoding technologies have enabled researchers to simultaneously profile gene expression, chromatin accessibility, and/or protein levels in single cells. However, these multiomic techniques often pose technical and financial barriers that limit their practicality. Kevin Wu and colleagues recently developed BABEL, a deep learning algorithm that can effectively translate between transcriptomic and chromatin profiles in single cells, thereby enabling researchers to perform multiomic analyses from an individual dataset.

The progressive loss of CD4 + T cells has been recognised as being central to HIV-1 pathogenesis, however a precise understanding of the underlying mechanisms and, consequently, improved therapies have yet to be achieved. Zhang et al. have recently shown in HIV-1 patients that the NLRP3 inflammasome pathway, which plays a key role in innate immunity, is a crucial mediator of the loss of CD4 + T cells. This advance could inform the development of innovative anti-HIV-1 therapies.

Climate change has been shown to affect the interannual variation and synchrony among individuals in seed production of masting trees, yet the proximate mechanisms driving these patterns remain unclear. A recent study by Michał Bogdziewicz and colleagues shows that the relationship between weather cues and seed initiation weakens in European beech as warming increases, resulting in progressive asynchrony of seed maturation. This study emphasizes the vulnerability of the relationship between environmental cues and forest reproduction to climate change.

Sepsis-associated encephalopathy, as well as increasing mortality, has been associated with long-lasting depressive behaviour, which is thought to be caused by infection-induced neuroinflammation in the brain. Saito et al. have recently demonstrated in a mouse model of sepsis that infiltrated regulatory T cells in the cerebral cortex mediate the resolution of neuroinflammation and alleviate anxious/depressive behaviour. Their study paves the way for further research that investigates the role of T cells in the underlying mechanisms mediating recovery of sepsis-associated depression.

While loss-of-function mutations affecting the α2-Na/K ATPase are known to cause familial hemiplegic migraine, it is unclear how reduced protein activity could contribute toward migraine or paralysis observed in patients. A recent study from Sarah Smith and colleagues demonstrates that conditional deletion of the α2-Na/K ATPase in astrocytes can evoke episodic paralysis in mice, potentially due to altered metabolic processing of serine and glycine. By feeding juvenile α2-Na/K ATPase mutant mice a serine- and glycine-free diet, the authors are able to prevent the onset of episodic paralysis. This study suggests that loss of α2-Na/K ATPase in astrocytes may affect amino acid metabolism in the brain, ultimately leading to episodic paralysis.

A huge amount of intrigue surrounds the aging process. Senescence—the decreased likelihood of reproduction and the increased chance of mortality—is a hallmark of aging. The reduced ability of senescent cells to maintain protein homeostasis (proteostasis) has been well-established in nematodes but this phenomenon had yet to be directly demonstrated in human cells. Sabath et al. recently provided compelling evidence that proteostasis collapse is indeed intrinsic to human cell senescence, which may have broad implications in the underlying processes of human aging.

Protein aggregation and phase separation appear to play important roles in diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD), but the interplay between different participating molecular events-which may facilitate or inhibit one another-can be difficult to study by conventional ensemble methods. In a recent study, Kevin Rhine and co-workers make use of point mutations to demonstrate the contrasting behaviour of condensates arising from Glycine and Arginine FUS mutants using single molecules fluorescence measurements.